go for the .22 cal pistol. i have a ruger super six with a 2-7 power scope and it is very deadly on squirrels. i also have ruger bear-cat that is great to shoot out to about 50 yards. also have a taurus pt-22 that i really like to carry in my training bag when we are out with the dogs. it is very easy to shoot and is a straight shooter. all of these .22 pistols will out shoot my 9mm and my springfield .45 at 45 to 50 yards. the only pistol that will shoot with the .22's that i have is my .scoped .44 mag. go for the .22 and you'll be very surprized how good you will get with it. i can shoot the .22's better justbecause i shoot them so much more than the larger calibers. years ago we would make the rounds to all the dumps in the area to hunt for rats and we all used .22 pistols. used to be good enough to have a sandwinch in one hand and shoot a rat with the other. man that was fun.
for defense it is better to hit what you are shooting at with a small caliber than to miss with a larger caliber. i feel very comfortable carrying a .22 pistol.