For me, my top favorite weapon has got to be the Dual Wielding Flare Guns in Timesplitters Perfect. The wild unpredictability of them at long range makes them a blast to use against friends because you never know who's gonna die and when. Plus the ability to set people ablaze is always wonderful.
Second has to be the 500 tactical shotgun from Rainbow Six Vegas 2. By far my favorite weapon in that game and just overall one of the best shotgun experiences I have had in any game. Last night alone I had a good solid 21 killing spree (and a huge thanks to my teammates for providing cover fire and watching my back for that).
What's your favorite weapon? Anything from Link's sword in legend of Zelda to the BFG from doom are welcome.