For SD against 2 legged animals, I carry anything 9mm and up. I have a pair of Glocks, on in 9mm and one in .40. As far as most powerful I own, that's a 1911 gov't in .45. The 10mm is one I really want to get soon in a full size package, and that has more energy than the others I have. .357Sig is an awesome round, but price is kinda restrictive. .50GI in a 1911 seems like a real winner though.
For 4 legged animals, I have a .44Mag with a 6.5" barrel that's good enough for anything south of a Grizzly, which means I should probably get a bigger gun since I live in MT. I've shot the .500 S&W, and I'm not a huge fan of the amount of recoil. I'd rather have a .454Casull with less recoil but I can get a follow up shot much faster.