Even though takedown of the MK3/22-45 may suck, it is, to me, the best designed handgun for 22lr, period.
I LOVE my dad's High Standard Victor, and it is SUPER accurate. But the damn thing sucks at feeding cheap ammo. I mean, it'll run CCI stingers all day long. But why would I buy something that's nearly the same price as 9mm if I'm not even hunting with it?
The Ruger system that they use is extremely unique. Rather than having a large reciprocating slide, they choose to use a cylindrical bolt. This keeps the function smooth, recoil low (although 22lr is already low), and malfunctions to a minimum.
The Browning Buckmark is also a great handgun. It utilizes a slide system that is nearly identical to the tried-and-true High Standard. It is also a great option.
The thing that jumps out the most to me about both of these handguns is the fact that they can have VERY THICK barrel profiles without affecting the function of the gun. This setup maintains exceptional accuracy, prevents heat from sapping away this accuracy, and prevents an entire slide from having to move a thick barrel.
An M&P22, Sig Mosquito, SR22, and P22 will NEVER outshoot one of these pistols... PERIOD. And the fact that these guns are around the same price range, I think the answer is even clearer...
Now as far as which of the two I would own, I would have to go with the Ruger since parts are more common. The 22/45 LITE that was previously mentioned is an amazing package. It includes a threaded barrel, a very light barrel-in-tube setup, and a picatinny rail to mount on top if you wish to add an optic. This gun with a 22 suppressor and a Burris Fastfire is the absolute best setup in my mind. (this picture plus a suppressor is my ideal setup) Image: http://ts2.mm.bing.net/th?id=H.4545781360625589&pid=1.7
I also would like to let you know that I would take a Buckmark too. It is a proven 22 and plenty of people love them. You can't go wrong.
Just remember... if you want a REAL 22, get one of these 2.