A .22 can definitely kill you...eventually. Coming out of a pistol it is even less powerful and a really bad idea as a defense piece. Recently I read about a guy who shot a home invader square between the eyes with a .22 pistol. The round didn't penetrate the guy's skull. In another case a guy shot a .22 rifle in defense at the center mass. The bullet bounced off a rib and rested in his chest. The BG drove himself to the hospital.
Sure, any caliber CAN be ineffective and pistol calibers are generally worse than rifle, but you have to stop somewhere. Otherwise you will be defending yourself with a BB gun and talking about how you heard stories of people getting killed with them so they are OK defensive weapons.
OK...rant over.
As for the choice, I'd go with either a Beretta Neos, Browning Buckmark, Ruger, or S&W 22A, in that order of preference.
Of all them I tried I liked the Beretta's trigger the best and it is, by far, the easiest to break down. You can swap the barrel in under a minute.
The Buckmarks are my second favorite...built like tanks and a bit more refined than the Ruger...and easier to clean.
The Ruger has the advantage of a huge accessory base. The trigger on the few I tried wasn't quite as good as the Neos or Buckmark. I've read that their quality isn't what it used to be.
I didn't take to the S&W's grip, but your mileage may vary there. It doesn't have the history of the others and did see some reports of some issues with some of them...not sure if those were teething issues that come with many new guns. The rest of the gun was impressive and S&W has the best customer service in the industry.
Guns like the Bersa .22, or the Walther P22, or the Sig Mosquito are fun but less accurate. They mimic the look and feel of centerfire autos which is something some people like (though the grip on the P22 is downright minuscule.)