I'm playing a stealthy character and have 3 weapons with me all the time. Sniper rifle for outdoors, shotgun for close combat and a missile launcher for the bosses.

Do Nuka grenades count because they're are a blast to use...no pun intended

An update from my earlier post having found the Terrible Shotgun.

This weapon is freaking awesome! Was exploring a building (spoiler-free) and while I was down below, a Mirelurk Queen decides to pop in for a visit (by the way, ever be on top of her burrow when she pops out? Quite the ride, I must say!).

Normally, I'd soil my underwear, run while crying like a little girl, but I turned the Terrible on her and she went down within 20 shots... NO VATS!

Yep, the Commonwealth is all mine now.

I also tried the Guass rifle. One-shot killed a Mirelurk Razorclaw. Nice weapon, but I don't have much ammo for it. I'll stick with the shotgun. It proved itself this evening.

I like it simple. I mostly use a hunting rifle 50 with all the options and glow sights with the explosive AoE mod. Then I keep a version with recon sight, another with long night site, and another with glow sights but no explosion mod for when I am in close quarters such as defending settlements, I don't have to worry about blowing up friendlies.

Big boy nuke launcher is the best "grenade" launcher in the world.

.45 combat rifle, lighter long barrel for sniping, powerful frame with iron sights.

Experiment 18-a modded as a plasmathrower.

The 45 cal combat rifle, advanced receiver(semi) with recoil stock and reflex dot. Best short med and long range rifle in the game. i still carry a combat shotgun for serious in your face stopping power, and a recon 50 cal for long range bell ringing but the combat rifle is what i lead with until a situation calls for another weapon.

I have a .44 pistol with a bull barrel I think it is and an advanced whateverI think and a reflex sight, that does explosive rounds.....Legendary ftw. =) People blow up nice.

-Light Combat (e.g. Raiders, Feral Ghouls): Railway Gun

-Heavy Combat (e.g. Sentry Bots, Assaultrons): Gatling Laser

-Close Combat (e.g. Some Melee Opponents): Flamer

-Initial Encounters with Heavily-Armored Foes (e.g. Power Armored Foes): Missile Launcher or Big Boy (Fatman with Additional Projectile)

the suppressed Walther you get from the helping the railroad great gun & it doesn't take up 3/4's of the screen

I always make sure to have at least one knee-capper on standby just because of those damn Assaultron Dominators.

I mostly use a fully modded Shotgun up close or a modded Sniper Rifle .50 cal at range, and the Assassin's Machete for melee.

The Deliverer. I can get over 15 shots off in VATS, each one adding 10% to its accuracy and gaining in damage as I hit more targets, so even though its range isn't great, so long as I can get someone highlighted in VATS, the accuracy for a head-shot quickly climbs up to 95. It's quick enough that I can pop off a pack of ghouls even without VATS and doesn't take long to reload. On top of that, it's silenced too, so the ghouls don't even know where I am!

Mine is actually the 10MM handgun, modded of course. Its the first Fallout game that I find it actually useful. http://chosenofmystra.com/images/f4/ScreenShot34.jpg

It'll take care of any muties, ghouls or raiders. I'll switch to a different weapon if the enemy is too strong, otherwise I carry it at all times.

Overseers Guardian modded with a .308 receiver, recoil compensated stock, long ported barrel, medium range night vision scope, and suppressor. I do a total of 5.3x sneak attack damge and it does 170 dmg and that's with out the last rank in rifleman , last rank in lone wanderer, and no perks in bloody mess.

Just put the strongest auto receiver on an assault rifle, recoil stock, quick-eject drum, and suppressor. That, accompanied by Commando 3, and this thing is a BEAST. Next to no recoil, and is just a jackhammer.

Two shot sniper rifle for those times I need to reach out and touch someone. Combat shotgun or 10mm for enemies up close, depending on their perceived strength. Spray and pray for those special bad guys.

I have a 10mm that does extra damage to limbs....

lots of ghouls with no legs in my game world.

For a while it was my plasma infused 10mm but I tossed it to my private dike companion.

Final Jugdment for my primary and Firefly ( legendary 10mm pistol w/ Fire damage)

I use the Wounding Piercing Hardened Submachine gun. Found it on a legendary super mutant. It's a 45 cal with 13 damage but gives 25 extra bleed out points. You only have to shoot enemies once or twice and then sit back and watch their life points drain away.

Ranged character: suppressed 10mm pistol, suppressed .50 sniper rifle. With the sneaky perks pretty much everything dies in one hit.

Melee character: I found a combat knife that does double damage when targets are at full health. I can take out entire groups in one VATS.

Lately I have been having a lot of fun using .50 cal reflex sighted hunting rifle - shoot and bash for encounters where I'm forced outta stealth. It has that satisfying powerful *BOOM!* shot sound.

My go-to gun is a penetrating .308 semiautomatic Combat RIfle with reflex sights.

Believe it or not, but my level 50 character primarily uses a modded automatic pipe rifle as the primary weapon on hard difficulty.

It does 28 points of damage, and has the 48 capacity drum along with some other mods.

Silenced 10MM - Wastelander's Friend that does 50% more limb damage (with recon scope). I use that gun most often. My 2nd one is a modded .50 cal silenced sniper rifle that does burning damage (also with recon scope) and then I also use my modded hunting rifle that does 50% more damage to animals. Besides that I have a .44 revolver that does 121 damage (advanced receiver) and a mighty shotgun that does 25% more damage.