Off the top of my head, I sure do like the infinite launcher in Resident Evil 4. It made me feel like I had so much power, without just being so OP it ruined all the fun, like the zappy gun.

"Why do you hide, stupid aliens? Mr. Zurkon only wishes for to kill you."

And all its variants.  

A Lightsaber. Pick your Star Wars game .

My two favorites.

teh fuckn flak cannon. best gun ever, it sounds great, it looks great, the gunplay is nice. and a shotgun with shrapnel grenade launcher as 2nd fire is just soooo badass

Omega Shock Cannon (Ratchet & Clank 3)

Sol Blade from Golden Sun. You can throw meteors with that.

Does Kazooie count as a weapon? No?

well then its going to be

My two favorites.

Excalibur