It's kind of like the once-popular .25 ACP, the favorite of pimps and related street scum for years (until they discovered that 9mm often does the job, and .22 LR is cheaper). Interesting thing about it is that while it has next to no stopping power -- shoot somebody with one and he's likely as not to get really pissed and beat you to death -- it has very high lethality. That's because people shot with one often don't take it seriously. They don't get treatment or anything. Not a good idea. Jeff Cooper told of a guy in a bad mood at a party who, stumbling across a .25 auto upstairs, stuck it to his head and pulled the trigger. Not thinking that he had been much injured, he put a bandaid over the wound and went downstairs and rejoined the party. Next day, though, he woke up dead.
Yup, a 9-shot Harrington & Richardson break-top revolver. Not a bad gun, actually. The rest that you had to say about .22s is the fevered fantasy of screenwriters that has gotten picked up popularly but isn't true. And yeah, James Brady was vegetized by the shot (which is why it isn't the favorite of assassins -- it didn't kill him with a head shot), and his wife Sarah became a strident anti-gunner thereafter.
(I should note that the OSS did fiddle with a High Standard .22 during the war, not because it is especially effective for assassinations, but because it could be effectively silenced.)