For me, nothing beats Unreal Tournament's almighty Redeemer. Aside from the launcher's tube taking up nearly half of the screen, the (player-driven!) rocket's devastating payload guarantees your ears will be imminently filled with that sweet "M-M-M-M-MONSTER KILL!" if used correctly.

The Farsight from Perfect Dark is the only weapon for me. It's extremely unfair and overpowered...but only if someone else has it. Why's that? Well, let's see:

1. It's X-Ray scope let's you see through walls.
2. It can shoot through walls.
3. It tracks enemies so you barely even have to aim.
4. It kinda looks like a dolphin.

All you have to do is hide in a corner and win.  

I'd have to say Quake's rocket launcher is my favorite. It's not only a weapon, but also a means of transportation. It's powerful enough that any novice can get a few kills with. But there is also enough of a learning curve that separates the skilled from everyone else.

The Magnetic Rail Driver from Red Faction II made splitscreen multiplayer an absolute blast. Not only could it shoot through walls, it also allowed you to (sort of) see your enemies in other rooms. 

I have two, but I'm not sure they count.

The portal gun from Portal was amazing. It turned everything into a weapon -- turrets, crates, yourself. That zweept-kweeer sound effect is one of the most satisfying sounds in a game ever. It's limited function allowed for an amazing array of challenges and puzzles.

The nano file from Red Faction: Guerilla unleashed the full potential of the game's unqiue destructable environments. It opened up any number of options when approach new areas, enemies, and tasks. Taking down a huge building with a couple well-placed shots is unbelievably satisfying.

(Why they may not qualify: Portal gun is not very shooty-shooty, while RF:G was technically an open world game, although it had some very awesome shooting mechanics -- the best in the genre.)

I've got a few:

Crossbow (Bioshock): Once you get ahold of this and upgrade it a bit, it becomes a huge game breaker. Specifically, some well-placed Trap Bolts can kill a Big Daddy in seconds. It's also a very satisfying weapon to boot.

Chemical Thrower(Bioshock): What's better than a flamethrower? One that can shoot ice AND electricity! A great replacement for those who don't wish to spend their ADAM on better plasmids.

Railgun(Quake II): It's a weapon that's just as powerful as, if not better than, the BFG and definitely blows the Rocket Launcher out of the water in sheer power. Turning Strogg to goo has never been so effortless.

Both Guns(Hard Reset): Only 2 weapons in an FPS may sound like a deal breaker, but when you realize that it's actually 5 radically different modes that you gradually unlock for each one, that's when the game shows its strong suit. And I didn't even mention the individual upgrades to those firing modes.

While it's tough to deny the vape-anything appeal of the alien raygun, I always found myself partial to Fallout 3's Lincoln Repeater. I loved the plesant little ping it made when you fired it...and its habit of blowing super-mutant heads clean off super-mutant necks.

My favorite gun is the Flak Cannon from the Unreal series. I'm an old-school Flak Monkey -- the primary-fire shards were perfect for up-close encounters, and the secondary-fire grenade was excellent for bouncing around corners.

Can we just add a whole Borderlands section? All the legendary weaponry in that game is fantastic. If I had to pick just a few though:

1. The Chimera: A revolver that self-alternates among electric, corrosive, fire, and explosive bullets? It's like a little surprise every time you shoot!

2. The Friendly Fire: A shotgun that has a pellet spread in the shape of a smiley face.

3. The Chopper: An assault rifle that shoots it's entire 500+ magazine with one pull of the trigger. Once you pop, the fun doesn't stop.

I have one gun that I'd like to add.

My personal favorite is still the M134 Minigun from Serious Sam: The First Encounter. I know that Team Fortress 2's minigun is the most famous, but the M134 could kill humongous dinosaurs. That gun had serious firepower behind it.

I was also going to suggest the plasmids from BioShock, but I figure it wouldn't count, because it has to be a gun.

Honestly, I still love the BFG for all my massive destruction needs. It's hard to beat that one, in my opinion.

I like the crossbow from Gears of War. It goes boom.

There's also the Fat Guy from Fallout 3. It's a mini-nuke, and makes things go boom.

There was also the M63 from Metal Gear Solid 3. It held a lot of ammo, and if Snake shot it for a long time he would start yelling, which was kind of cool.

Finally, the PEPS from Deus Ex: Human Revolution was great. It was a non-violent gun that fired a short range pulse that could knock multiple people off their feet and could result in take downs. It was fun to use, and since  I wasn't going for a non-violent playthrough, so I just tossed people up with the PEPS and gave them headshots with my pistol when they were on the ground.

I'm with Sam the Farsight is one of my favorite guns of all time. But I think the taser from Syphon Filter deserves a mention. Nothing like tasing a badguy till he catches fire. I'm also a sucker for anything minigun related. 

Some great memories here!  Loved the cerebral bore, and all the launchers from ROTT.  Although the bio-rifle... I always hated that gun, haha.  Not that it wasn't cool, but it was just less powerful than half the other guns.

Well there is the RC-P90 from Goldeneye. But I guess that is close to a real weapon right?

More Stranger's Wrath representation on this list! Although I didn't really play it so I won't be the right guy for specifics.

When I think of guns I like, instead of out-there weaponry, I think of normal guns that are beautifully designed or feel good to use — with some meat and power behind them. A few favorites off the top of my head are:

1. Hammer from Crysis 2 (pretty much a Desert Eagle)

2. 10mm Pistol from Deus Ex: Human Revolution

3. Combat Shotgun from Fallout 3

4/5 - The custom shotgun from Hitman: Blood Money and the Marshall shotgun from Crysis 2 because they have silencer attachements, No-Country-for-Old-Men style.

6 - Any shotgun from the FEAR series. Get close enough and your enemies erupt into a cloud of blood.

If not the Cerebral Bore, it must be the Chronoscepter (Turok 1). It may look lame nowadays, but in its prime it looked as if the entire world blew up (at least for a second). Plus, the laser could bounce dead bodies around after you already "obliterated" them.

When you say BFG, I assume the 9000 from Doom, but don't forget about the 10K from Quake 2. I likes it for the "leaks" from the main beam that devistated anything is came across.