Well, if we're talking caliber, I'll take a .50. Just like the one Steve Railsback's character carried in Armed & Dangerous.
The .50 suffers from several flaws, all centered around the fact that it's too big and powerfull to be an effective combat cartridge.
Pistol cartriges in the .40 to .45 range are the perfect comprimise between size and power.
A rimless version of the .44 special (which is in reality, a .428) would be an ideal combat cartrige.