i dont recommend a .22, at all for self defense. simply not enough stopping power. unless its a well placed shot, its not going to be a cut and dry stop.
how large are you hands? this plays a big role in being comfortable with a handgun.
also, i strongly recommend a glock. virtually maintenance free, fairly cheap, very reliable and easy to shoot well.
for me, i shoot better with a glock .45 than with a .40. simply put, the .45 fits my hands better, and the recoil is more of a "push" than a "snap".
based on that, i would choose on of the two above. i have shot more handguns than most people have/will, and i still go back to the good old glock. I trust my life with my glock .45 every day, and feel confident in doing so.
edit- based on that you want it for only home defense, a shotgun is very hard to beat. very good stopping power, and you only have to get "close". i would recommend a 870 remington....
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2009 PW Sport/Touring/Nav M6
Stillen Gen 3 Intake/CBE/Berk HFC/BC BR Coil over/Phillips 6500k/Hotchkis Sways/Stillen oil cooler/B&M SS
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