Id go with some think like a S&W x-frame revolver. those 500 magnums are pretty slick stuff.
For a semiautomatic I would go with one of the automags out there. Desert Eagle, L.A.R., Coonan, Wildey just to name a few.
Shot placement is everything! I would rather take a round of 50BMG to the foot than a 22short to the base of the skull.
all 26 of my guns are 45/70 govt, 357 mag, 22 or 12 ga... I believe in keeping it simple. Wish my wife did as well...