When you do manage to shoot them (without getting shot first) it's all physics. Variables like how close you are to a vital organ, how fast the bullet is travelling, how big/heavy the round is all come into play. Also how big the attacker is, how much clothing he's wearing etc.
Of course there are very specific scenarios where a .22 could be considered (close range quiet kills etc.), but anyone who advocates a .22 as a general purpose self defense round is nothing less than an abject moron.
Bad guys don’t stand around at close range waiting to be shot. They flail, hide behind things and often shoot back with large caliber rounds.
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The most popular caliber carried by criminals is .380 auto. In really poor neighborhoods they prefer even smaller.
That said, I've also seen folks who simply can't manage anything bigger than a .22lr -- step 'em up to a .38 special or 9mm and the blast and recoil have them all over the target. For those folks, a .22lr is a fine choice, particularly those 8-shot revolvers with some CCI Stingers or Velicitors.
And don't even get me started on the .22WMR -- that 30-round pistol that Kel-tec sells would be hell on wheels. That's a lot of kbang for one magazine. $:-)