How much are you looking to spend and how much are you planning to use it?
If it is solely for home defense, get a .40 or .45. But if you plan on going to the range with that gun a lot, you'll go broke shooting real quick. If you want range use and home defense, I'd prob go with a 9mm and save some $$ on ammo.
A .22 is real cheap to shoot, but there's a good chance you'll die during a home invasion.