I've been trying to play Skyrim for about two weeks now. The operative word being 'trying'. I started off with following the STEP guide and then adding a few extra mods I wanted to try out, like TAZ enb, Archery Gameplay Overhaul, Mature Skins, iNeed and Camping.
The game was very unstable. I'd crash fairly frequently, especially in cities, always outdoors or while entering and indoors location. Never related to specific activity or action, never indoors unless in the process of going outdoors.
I scoured the internet for solutions. I settled on the idea that Skyrim cannot access more than 3GB of memory, any attempt to do so will cause the client to crash or freeze. I began to run Skyrim with windows performance monitor running in-order to ascertain if this was the cause. It was, or at least I think it is. When it was crashing originally Skyrim process was displaying 3.1GB of RAM in use. After configuring enb to take some of the load off it would still crash and still does crash when both processes combined reach that number or an approximation of it. For example, enbhost will read 2.2GB while Skyrim will read .9GB.
Further observations are as follows. It doesn't necessarily crash in any particular area or on any particular save. I can crash in one area one time, but not crash entering the same area a second time. It most frequently happens when entering a building in a city, with or without city altering mods enabled or when wandering close enough to cause a city load in more detail than LOD.
I've reinstalled Skyrim after uninstalling it, deleting the directory, my documents folder and cleaning the registry.
I've tried more witchcraft and .ini tweaks to skyrimprefs, enblocal and skse than I care to count.

Here's my current load order.
# This file was automatically generated by Mod Organizer.
Skyrim.esm
Update.esm
Unofficial Skyrim Patch.esp
Dawnguard.esm
Unofficial Dawnguard Patch.esp
HearthFires.esm
Unofficial Hearthfire Patch.esp
Dragonborn.esm
Unofficial Dragonborn Patch.esp
Skyrim Project Optimization - Full Version.esm
HighResTexturePack01.esp
HighResTexturePack02.esp
HighResTexturePack03.esp
Unofficial High Resolution Patch.esp
Cutting Room Floor.esp
SPTConsistentOlderPeople.esp
dD - Realistic Ragdoll Force - Realistic.esp
SkyUI.esp
MatureSkinComplexions.esp
Better Embers.esp
Smoking Candles.esp
Smoking Torches.esp
Guard Dialogue Overhaul.esp
Weapons & Armor Fixes_Remade.esp
Clothing & Clutter Fixes.esp
Weapons & Armor_TrueOrcishWeapons.esp
DeadlySpellImpacts.esp
aMidianBorn_ContentAddon.esp
imp_helm_legend.esp
Book Covers Skyrim.esp
SkyFalls + SkyMills + DG + DB.esp
Beards.esp
Brows.esp
Elemental Staves.esp
GQJ_DG_vampireamuletfix.esp
dD - Enhanced Blood Main.esp
dD-Dragonborn-Dawnguard-EBT Patch.esp
dD-Reduced Splatter Size.esp
dD-Reduced Wound Size.esp
SkyFalls Dragonborn Small waterfalls.esp
Point The Way.esp
RealisticWaterTwo.esp
RealisticWaterTwo - Legendary.esp
milklegendary.esp
TradeBarter.esp
SMIM-Merged-All.esp
SFO - Dragonborn.esp
SkyrimImprovedPuddles-DG-HF-DB.esp
Skyrim Flora Overhaul.esp
PilgrimsDelight.esp
BlockSparkles.esp
BretonLongbow.esp
WondersofWeather.esp
realrain.esp
Rainbows.esp
Better Dynamic Snow.esp
Footprints.esp
mintylightningmod.esp
dD-No Spinning Death Animation Merged.esp
randomthunder.esp
Soul Gems Differ.esp
iHUD.esp
RUSTIC SOULGEMS - Sorted.esp
CinematicFireFX.esp
ExplosiveBoltsVisualized.esp
Vividian - Weather Patch Vanilla.esp
Vividian - Extended Weathers.esp
Skyrim-Mapweatherfix.esp
Vividian - Torches Preset.esp
Bashed Patch, 0.esp

Here's ,y mod organizer mod list:
# This file was automatically generated by Mod Organizer.
+Bashed Patch
+Vivid Clouds and Fogs
+Vividian - Weather and Lighting Enhancement - 7
-TAZ lighting DLC
-Follower Mod
-RS Children Overhaul
-Farm Animals - iNeed patch
-Farm Animals
-JKs Skyrim - All in one
-iNeed - Food, Water and Sleep
-Hunterborn
-Traps Make Noise - More Dangerous Traps
-Skyrim - Enhanced Camera
-Dig Site -- Relic Hunter Tents for Campfire
-Campfire - Complete Camping System
-Even Better Quest Objectives
-Wiseman303's Trap Fixes
-When Vampires Attack
-Wet and Cold
-Skyrim Coin Replacer Redux
-Run For Your Lives
-Non-Essential Children
-Lock Overhaul
-Archery Gameplay Overhaul - Enhanced Camera Patch
-Archery Gameplay Overhaul
-Wintermyst - Enchantments of Skyrim
-Complete Crafting Overhaul Remade - Patch WAF True Weapons
-Complete Crafting Overhaul Remade
-ABT - Arrows and Bolts Tweaks
-Ordinator - Perks of Skyrim
+Retexture for Be a milk drinker
+Be a Milk Drinker
-Audio Overhaul for Skyrim 2
+Immersive Skyrim Thunder V6
-Immersive Music by Hothtrooper44
+Fores New Idles in Skyrim - FNIS
+New Animation for Magic Casting - New Animation for magic cast v0-8
+Faster get up animation
+Better Turn Animation
+No Spinning Death Animation
+Better Jumping
+No heavy muscular walk and idle
+Animated Clutter
+Lightning during Thunder Storms
+Point The Way
+Skyrim Improved Puddles - SIP
+Footprints
+Realistic Water Two - ENB Textures
+Realistic Water Two
+The Ruffled Feather
+Rainbows
+Real Rain
+Wonders of Weather
+Improved Weapon Impact
+Finer Dust
+Enhanced Blood Textures
+DROPS
+Frost Atronach HD Retex
+Bellyaches HD Dragon Replacer Pack
+Bellyaches Animal and Creature Pack
+Real Bows Lite
+Breton Longbow
+LeanWolf's Better-Shaped Weapons - All in One Installer
+Greatsword Sheaths and Scabbards Redux
+Dawnguard Crossbow Explosive Bolts Visualized
+Closer Quivers and Longer Arrows
+Elemental Staffs
+RUSTIC CLOTHING - WIP
+EASIER LOCKPICKING - Without Cheating - Nordic Retexture
+RUSTIC WINDOWS - 2K and 1K Textures
+PELTAPALOOZA - Pelts of Skyrim Expansion
+RUSTIC SILVERWARE
+RUSTIC POTTERY
+RUSTIC DINNERWARE
+RUSTIC ALCHEMY and ENCHANTING TABLES
+RUSTIC CLUTTER COLLECTION
+RUSTIC COOKING STATION
+RUSTIC SOULGEMS
+Gemling Queen Jewelry
+Septim HD
+White Phial Replacer
+Silly Level of Detail - Wine Cellar -- SLOD WC
+Silly Level of Detail - Potions and Poisons -- SLOD PnP
+Super Realistic Ore Textures
+Soul Gems Differ
+HD Ore And Ingots
+Book Covers Skyrim
+High Quality Food and Ingredients
+Gemling Queen Dragon Claws
+Detailed Rugs
+New Jewels for Circlets
+Barenziah's Glory
+Smaller Ice Spike and Ice Spear
-Ultimate Spinning Arrows - Immersive Weapons Patch
+Ultimate Spinning Arrows - Closer Quivers and Longer Arrows
-Ultimate Spinning Arrows
+Sweet Mother - the Night Mother Improvement
+Designs of the Nords
+Roadsigns Redone
+N-R HD Display Case
+Visible Windows
+Pilgrims Delight - High Hrothgar Shrine Retextures
+The Beauty of Skyrim - Dungeons
+Re-Defined Dungeons WIP
+aMidianBorn Caves and Mines
+aMidianBorn Whiterun
+aMidianBorn Blades Armor
+aMidianBorn Bonemold armor
+aMidianBorn Imperial Forts
+aMidianBorn stormcloak officer armour
+aMidianBorn Farmhouse
+aMidianBorn farmhouse and roads stonewall
+aMidianBorn Solstheim Landscape
+aMidianBorn imperial light and studded
+aMidianBorn Blade of Woe
+aMidianBorn Book of Silence - Content Addon
+aMidianBorn Book of Silence - Weapons
+aMidianBorn Book of Silence - Unique Items
+aMidianBorn Book of Silence - Dragonborn DLC
+aMidianBorn Book of Silence - Creatures
+aMidianBorn Book of Silence - Armors
+Smoking Torches
+Smoking Candles
+Deadly Spell Impacts
+Better embers
+Ultimate HD Candle Flames
+Cinematic Fire Effects 2 HD
-Ultimate HD Fire Effects
+Enhanced Night Skyrim
+SkyFalls + SkyMills
+Skyrim HD - Riften
+Skyrim HD - Towns
+Skyrim HD - Misc
+Skyrim HD - Landscape
+Skyrim HD - Dungeons
+Skyrim Flora Overhaul
+Ruins Clutter Improved
+Static Mesh Improvement Mod
+Natural Eyes
+Better males
+Mature Skin 2
+Brows
+Beards
+Immersive HUD - iHUD
+Main menu texture and music replacer - Windy Malukah
+Better MessageBox Controls
+Better Dialogue Controls
+SkyUI
+Female Vampires Have Fangs
+XP32 Maximum Skeleton - XPMS
+Realistic Ragdolls and Force
+Weapons and Armor Fixes Remade
+Trade and Barter
+Skyrim Project Optimization
+Improved closefaced helmets
+Guard Dialogue Overhaul
+Enchantment Reload Fix
+Cutting Room Floor
+Consistent Older People
+Clothing and Clutter Fixes
+Unofficial High Resolution Patch
+Unofficial Dragonborn Patch
+Unofficial Hearthfire Patch
+Unofficial Dawnguard Patch
+Unofficial Skyrim Patch
*Unmanaged: Dawnguard
*Unmanaged: Dragonborn
*Unmanaged: HearthFires
*Unmanaged: HighResTexturePack01
*Unmanaged: HighResTexturePack02
*Unmanaged: HighResTexturePack03

and here's my PC specs,
Intel i5-4670K @ 3.4GHZ
Windows 8.1 Pro x64
16GB Corsair Vengeance DDR3
eVGA Nvidia GTX 980Ti @ 2560x1440 144mhz

How does it perform without mods.

It is best to install one mod at a time and test it out and continue from there.

Thank you for the reply.

Funny story... Skyrim won't actually function without at least enb installed. Without it, the games' FPS are too high and the horse doesn't survive the intro scene long enough for me to escape. I have to install at least enb to limit the frames and with that, and only that, I've been able to fly around the world without any crashes.

I think it is due to your monitor since the game does not play well at FPS higher than 60 and it is usually best to cap it slightly lower than 60. I think it is the physics engine gets all wonky at 60+ FPS.

How does it run with only the ENB or ENBBoost portion of it. I personally do not use an ENB or ENBBoost but then I do not use that many mods and I do not use that many graphics mods and I usually6 have the game capped at 30 FPS.

I have the game capped at 60 FPS using enb. If I'm using just ENBoost, for the frame cap - it's fine.

Disabling JK's Skyrim and Expanded Towns and Cities enabled me to tgm, tcl, player.setav speedmult 1000, set timescale to 500 and then fly to each major city plus Falkreath and load into the inns without crashing or hanging.

JK is likely more of a performance hit due to all the clutter the mod adds, especially if using hd texture replacers for clutter and such. As for Inns it might be an issue with ETaC inns if using the inns option and another mod that makes changes to inns. You might need a compatibility patch(es)

I thought that disabling SMIM would do it, but it didn't.

I'm not really using any large-scale high resolution texture mods and if I was it shouldn't be a problem for me unless it was just a problem for everyone.

I'm using JK's Skyrim Major Cities Only and Expanded Towns and Cities Complete. They shouldn't conflict, should they?

You know ive been on here thru out the years wanting help with crashes and what not.......a lot of people said to uninstall all mods and re-install them 1 at a time and go from there....im playing with a 100+ mod playload and i never did that i just kept fooling around with till i figured it out or someone told me a good suggestion.

I used to use enboost quite a bit but i was having problems and someone said to not use it..i think i was messing enboost inis up so i quit using it and sure enough became more stable for me......cant you set the fps to 60 fps with just the standard inis that ship with the game.

Some of the tools i use that i feel help me out alot is:
LOOT

TES5Edit

Mator Smash(i choose to use it cuz ive not had problems with her yet that ive noticed anyways.

And last but not least if you can kind pin point the trouble to 1 or 2 mods go to the nexus threads and read the comment there...ive found answers after digging a while.

Pretty much agree with what Qwert said, but with a slight caveat: the "best practices" recommendation of "Uninstall all mods and then install one at a time" is also useful in 'partial' form.

Meaning that, if you have a set of 50 or 80 mods that you have a strong "instinct" are NOT a part of your problem, just uninstall all the other ones, and then follow the "install one and play/test . . . repeat" best practice.

I have often been able to correct major game crashing problems by uninstalling a dozen mods, with a strong suspicion of which ones might be 'culprits,' reinstall them in order reverse to their suspiciousness, and by that method isolate the one that IS actually causing problems.

The other steps that I've found are quite useful:

After installing, using LOOT or some other app (Wrye Bash can evidently do it, and maybe NMM as well) to sort the load order. Then use Wrye Bash to make a Bashed Patch. I don't fully understand what that means, but I can observe that it makes the game run better!