This machine would be my pick.

ME: Gauss Rifle. I'm surprised nobody else has mentioned this gun.
RP: Hunting Rifle (with scope. Its simple, but so awesome.)

Riot Shotgun.

PAT-PAT-PAT-PATPAT-PATPATPAT-PAT-PAT.

/soundeffect

Riot Shotgun. This is what I bought into Zion. I ran out of ammo by the end, but that's user error, not the gun.

Seriously, this is so versatile. You can't snipe with it, but slugs and 10 rounds, it makes for a good carbine-class weapon, while keeping its main role of heavy close quarters dominance.

I see this as the list of viable "do-all end-all" guns that you could completely rely on, if you had to:

-Medicine Stick
-Holorifle
-Tri-Beam Laser Rifle (GRA)
-Survivalist's Rifle
-Lucky
-A Light Shining In Darkness
-Light Machinegun
-Bozar



The Medicine Stick, Holorifle and Survivalist's Rifle have a nice combo of hitting hard while still firing fast. The only issue I could see with these is, speaking from experience, you MAY have difficulties surviving the Big Empty with the Medicine Stick alone (ammo becomes an issue despite the fact that Lobotomites drop .45-70 Gov't), though I'm betting it could be done. I can also imagine there are points where the weight of Microfusioncells becomes an issue for bringing enough ammo with you to some places when using the Tri-beam laser rifle or Holorifle.
The Survivalist's Rifle is probably the most well-rounded one on that list. Damage isn't spectacular, neither is ammo availability, but it can get [censored] done.
Lucky and ALSID are more than capable of being stand-alone weapons, despite being pistols. Again, speaking from experience, it was Lucky that saved my ass when all my other guns were running out of ammo in the Big Empty. .357 rounds are arguably -THE- most common rounds in the Mojave, and as long as a character with a nice crit rate is using it, Lucky's crit damage makes up for it's otherwise low base damage. Lucky to be Alive and Better Criticals can make it even MORE deadly, to the point where the gun is capable of hitting over 1000 damage in a single shot. Lucky's one weakness is a rather slow reload speed. ALSID on the other hand does much of the same, but ammo for it is DEFINITELY an issue, weighing a decent amount and never being found in containers, as it's not native to the Mojave.
The LMG and Bozar are both high DPS weapons that can wield every ammo type: armor-piercing, hollow-point and custom load. Though you won't be able to snipe like you would be with the others (yes, even Lucky and the Tri-Beam can be used for sniping, dunno about ALSID), this gun can handle groups of people and it can take out enemies pretty quick. The Bozar vs. the LMG is simply preference.


Personally?
I'd choose the Medicine Stick or Lucky. TBH I'd have a tough time choosing between the two given my experience with the Big Empty, though yeah, I'd probably end up choosing the Medicine Stick if forced to choose. I'm sure either would work though.

Because it svcks and does close to no damage with a Energy skill of 70+

I'd use a light shining in darkness because:

-It does a fair amount of base damage (Proven by barely using any other weapon for 5 levels on medium difficulty and having hardly any problems with it)
-It's an accurate, short to medium range weapon
-It has a fast rate of fire
- low AP cost

the only downside I can think of is it's magazine size of 6.

The CZ56 avenger is pretty good too as long as you have unlimited ammo.

Also depends on your level, when starting OWB. I went there around level 35, they were carrying Hunting Rifles instead of Brush Guns.
So they dropped .308 instead of .45-70.
Bad times for someone with a Brush Gun/Medicine Stick.



Optimzed MFCs is the way to go then and Pack Rat as a perk to take. That will solve any weight problems.
Still, the Tri-Beam requires a lot of attention, as it wears down pretty fast even with the durability mod installed.
But I have to say, it was my weapon of choice in OWB whenever things got really hot, was so glad to have it with me there.



I think That Gun is all around superior to Lucky.
5.56 is easier to get by in quantities than .357, and gives you more choices with .223, HP, AP and Match rounds. and most importantly, it doesn't take a decade to reload.
Regarding OWB, I went there not knowing carry weight wouldn't be an issue, so I arrived with Gobi and 120 JSP rounds, a Tri-Beam with 300 bulk MFCs and That Gun with 70 .223s and 60 5.56APs.
So, ammo appeared to be a potential problem at the beginning, until I started converting the crap out of anything I could grab or buy.
5mm deliver Lead, Primers and Powder for 5.56, .45-70 do the same for .308 rounds, and I turned every SEC, ECP and MFC I could get into optimized MFCs for the Tri-Beam. That worked out pretty well, and I left with much more ammo as I had on arrival.



Playing through the whole game with one of these? Dunno. .45-70 is quite a rare caliber still, even if you happily brake down other ammo, .45.70 cases are quite a bottleneck.
And Lucky isn't that awesome, when you have to reload it during a battle or facing high DT enemies.
I really like Lucky, it is my early game sidearm of choice, but I always replace it with the more versatile That Gun, once my Gun Skill and STR meet its requirements.
A .308 chambered rifle, ideally Gobi, and a 5.56 pistol, preferrably That Gun, just seem more viable to me

You have to realize that the right build is neccesary for ALL of these guns. For example, low luck or low agility is gonna find Lucky absolutely worthless.
The reason I named those specifically is simply because if you DO build yourself around those guns, they're ideal. The build is very important.
For example you compared Lucky and That Gun. I used Lucky instead of That Gun because I had Fast Shot (Lucky has lower spread and I prefer it's ironsights, which are very good), because I had Hand Loader and personal experience told me that being able to interrupt the reload animation and that extra bullet in the clip actually mattered; I remember multiple instances in Old World Blues where I had to run from swarms of Nightstalkers and reload multiple times, and sometimes being able to interrupt the reload sequence of having 6 shots was life-saving. I'd also personally choose it over That Gun simply based on the fact that Old World Blues offers only .44 and .357 bullets. Either way, yeah, That Gun could be added to that list.

True that. It's just that That gun is very similar in that regard. They share the same base damage and have the same crit multiplier.
They just scream to be compared


My feeling was always like it takes you just as much time to do a full reload of That Gun, as you need for 1 or 2 rounds in Lucky.
For the Nightstalkers I have to admit, I was usually not taking any chances and relied on the Tri-Beam. Used That Gun more for Robots and Lobotomites



I entered OWB blind without knowing what would be available and what not. And while indeed .357 and .44 are pretty dominant, you can snag up a halfways decent number of 5.56, too.

I don't really see a need for any other weapon in the game after the Holorifle. I can snipe, I can hit mid range and up close. Plus it turns svckas to ash. Win. I make myself use other weapons just to say I have used them. Christine's COS Sniper and the YCS/186 are badass too.

The Tri-Beam laser could be good to take, as long as ammo was plentiful

Mercy.
With my stockpile of 40mm Plasma, its a sure thing!

One wepon no deteration and unlimited ammo would be the tesla cannon

Dynamite

While not very effective, and sure I tend to drop half of them at my own feet it would still be a rather hilarious game... even if it was a short one. Heck I think I will give this a try!

It's currently the Ratslayer. Silenced, great at long-range, easy to find ammo for, and it's light weight.

Hunting Rifle

CZ57 Avenger for the vanilla game and The tri-beam laser rifle (GRA) for the DLC. The CZ57 uses 5mm rounds. The armor piecing ones will do -25 DT. But it easy to run out of in OWB. Vigilant Recycler is better than Hand Loader in replacing ammo.

Anti material Rifle even its a Sniper its my most favorite Weapon in the game and i really own with it and it gives awesome slowmotion kills!

Hunting Rifle with all of the mods.

After messing with it, my choice is now MF Hyperbreeder Alpha. That gun is insane, and you never have to worry about ammo. Talk about travelling light!

45. Auto SMG is my favorite by far. That + Gambler Hat + Authority Shades + Pre-War Business Wear = Pure Awesomness. Of course if we're talking practicality than Marksman Carbine.

Hmmm....

Probably Li'l Devil. With a good build of course.

Fat man. If I could have unlimited ammo of course.

Cowboy repeater fully modded