I've got to admit that the Holy Hand-grenade would be an excellent choice, particularly when it's a Monty Python reference.
But believe it or not, mine would have to be the Chicken Drumstick, from Medievil 2. I'm unsure of its power, but I think it explodes after a time or it distracts enemies. Who the Hell cares anyway, it's a chicken drumstick! If not that, then the Hammer of Thor from the same game, which does Area of Effect damage and squashes enemies to look like they've been run over by a steamroller, OR the Gatling Gun from Medievil 2. Tough choices to make.