Rail Gun - Quake 3 Arena

Flak Cannon - Unreal Tournament

I just realized that I tend to prefer the standard weaponry, making my list kind of bland:

Halo - Assault Rifle
Dead Space - Plasma Cutter
Perfect Dark - Falcon 2
Mario Kart - Green Shell
Metro 2033 - Bastard Gun

But then there's also:

Metroid Prime - Annihilator Beam
The Legend of Zelda - Bombs
Banjo Kazooie - Explosive eggs
Goldeneye 007 - D5K Deutsche
Quake - Railgun

The mirror shield to me is a weapon. And the Duke Nukem Shrink ray.

The stellar converter from Master of orion 2, it disintigrates planets, nuff' said

ppsh-41  in Call of duty waw

Gonna have to go with the Windwaker version of the Light arrow:

Close runners up are the seismic charge from Rogue Squadron III & the Tsubaki MkIII from No More Heroes

The one and only: Zero Point Energy Field Maniuplator! Also known as the Gravity Gun

The Magnum from Halo: CE and Halo: CEA. The pure power that thing had.

Obviously... the incredibly overly flashy Ultima Weapon from Kingdom Hearts.

I'm PSYCHED!