Since the vast majority of us would be quite happy hunting only N. America with a handgun. I think a 45 colt pushing a 280-340gr. Bullet at 1200fps would handle adequately any animal on this continent. I do think an appropriate jacketed bullet would do better for most of us, but a cast bullet can and will kill game all day long.
I personally shoot 280s and 340s from my 5.5 guns, and feel adequately armed for my hunting grounds,......that said, I get a lot of enjoyment from using more than enough gun. So I do tend to carry .510 guns, but my 45 colts are very good general purpose handguns.