I agree that a .22 rimfire is much better than angry words, but it does have limitations. (as does ANY handgun cartridge)
There have been amazing success stories of self defense with the .22, and some pretty abysmal failures. I have heard quite a few times of a bullet striking the forehead, and not penetrating the skull. Of course, I would think that would at least slow someone down.
The biggest problem with any handgun is that there simply isn't enough trauma/shock at impact to put a person down immediately, consistently. The only thing that will do that is a hit to the central nervous system... brain/spine.
There are authenticated stories of widely differing results... a guy getting shot in the back 5 or 6 times with a .45 ACP, and he walked to the ER and got patched up. Then there is the video of a state trooper that got ambushed during a night stop, when there was a gunfight, the bad guy had a .22, and the trooper had his state issued semi... I think it was a .40 Glock. He shot the bad guy several times, who then rolled down an embankment. The trooper called in the shooting, then started weaving a little, sat down, leaning against the bumper, and died. He had been hit one time... straight through the heart, at the START of the gunfight, but had continued on for 5 or 6 minutes until internal bleeding took him down.
The bad guy was taken to a hospital, and survived.
I have a couple of .22's that I would trust with my life. I know what I am capable of at close range. A flurry of little .22's in the face would, no doubt, at least slow an attacker down enough for me to either get away, or get a bigger gun.
sounds like your wife should be in a pretty good position to defend herself. Personally, I'd rather see her use a Taurus TCP or the new Spectrum in .380. Same number of rounds, but WAY more effective for defense. The Spectrum is on sale several places for around $160.