Fat-Man Nuke Launcher - Fallout series. I'd use it against smaller groups approaching from the distance or far off fire-fights.
Gauss Rifle - Fallout series. Any instance I'd snipe, this'd be my go to weapon. So cool.
Super Sledge - Fallout series. Badass close range weapon.
Meteor - Final Fantasy series. I assume spells count, and for a wide-spread group nothing seems quite as devastating as this.
Summons - Final Fantasy series. I'd be perfectly happy with FFVI Advanced's pantheon.
Zodiac Spear - Final Fantasy XII. Spears are awesome. This is pretty much the most broken.
High Frequency Blade - Metal Gear Solid 2. As far as melee weapons goes, this would be a decent choice. As long as I have cyborg enhancements, anyway.
The Patriot - Metal Gear Solid 3. Useful for closer range gun-play, never runs out of ammo.
Magatama - SMT: Nocturne. Well, it'd be gross as hell to ingest. But demonic powers are pretty sweet.
Claimh Solais - Castlevania series. Coolest sword I've seen in a game.