I personally would not hesitate to use a .22 for home defense, although it wouldn't be my first choice. My first choice for middle-of-the-night scenarios is the pump 12ga. I keep the mag loaded at all times, and the action locked, with no shell in the chamber. My finger automatically hits the bolt unlock button when I grab the gun, and I work the action, filling the chamber with 00 buck. I hope the noise of the action alone will make the decision for "fight or flight" for the perp.
If the only gun I had was a .22, I wouldn't feel unprotected at all.
I always felt that if I got to the point where I thought it was time to bury my firearms, it was actually time to pick them up..