The vast majority of self defense situations don't require a shot to be fired. They require a gun to be brandished (with intent, and authority). You think that the villain looks at your gun and says "Oh, I ain't scared, that ain't a .45"??? If he was even that smart, he probably wouldn't be the villain in the first place. So - a .22lr pistol would do it's job admirably for something like 90-95% of all encounters - the ones where no shooting is necessary. And no, a replica doesn't work because YOU know its fake and the villain MAY recognize it, and certainly sees it in your wimpy demeanor.
If shooting IS necessary? Well, 22lr is the most deadly round in the US. More people killed with .22 than any other round.
As far as the old "stopping power" myth - the reality is that virtually none of the pistol calibers have such significant stopping power (or lethality, for that matter). I can't link to the study right now, but there was a pretty large one done in the US with police reports correlating caliber and number of shots to aggressors giving up their attacks (literally, "stopping an attack or advance"). The first thing is that on average it took at least 2 hits from either a 9mm or 45acp before the attacker realized he/she had been shot. That seems to be important - adrenaline and the mind plays a big part in "stopping power." For .22lr it took 3 shots. Yup - on average you had to shoot an aggressor TWICE with that big, powerful 45acp or 3 times with wimpy .22lr before they realized they were shot and started to think "hey, this sucks!"
If memory serves, the study found that those 2 shots of 9mm or 45acp, or 3 shots of 22lr, stopped roughly 70% of attackers. So those other 30% required still MORE. But from a self defense situation, you are now talking about stopping 70% of the 5% who weren't deterred by the mere presence of a firearm. And your likelihood of being in that situation isn't that high in the first place, unless you are talking military or police.
I won't touch the urban legends of the PCP-heads, as eventually people will be claiming that, like Superman, they survive multiple point blank shotgun blasts, 100's of rounds of 223, and several LAW rockets.
And if we are talking home defense from invaders, a study of inmates in the US found that they were more afraid of a homeowner wielding a machete than a firearm. Apparently many couldn't imagine being shot, but they could easily imagine being cut/hacked. I think it comes from watching too many stupid Hollywood movies. The upshot is - meet a home invader with a gun in one hand and a machete in the other. Assuming any response other than lubricating your butt and bending over are legal in Canada.