FrankenCub
.338 Win Mag
Having shot several thousand rounds through one of these, I wouldn't pass one up for defensive use. Extra thought required for how you're going to conceal it though. Winter isn't a problem, and good HD gun too.9mm: 124gr HST
.45 ACP: Federal Hi-Shok 230gr JHP
9mm I chose after looking at Lucky Gunner's testing - consistent penetration to the far edge of the FBI window and uniform expansion.
45 was just a cheap hollow point and isn't really a serious option for defense. I never carry 45 and the 9s would be the first choice in any home defense situation.
I don't even consider the other two calibers in a defensive capacity because the 357 is a revolver and the 22LR is, well, 22LR.
ETA: Link to Lucky Gunner data
Magnum Research Desert Eagle .357 6
My BIL had a nickel plated DE that I shot a LOT. For such a big heavy gun they sure are pleasant to shoot. If your hands are big enough.