I've had a Ruger 10/22 since the mid-90's. I probably have around 5000 rds through it, but I could be off by a factor of two. I'm mostly happy with it, but not 100%. I get a lot of jams with various types of ammo, and find I have to clean at least every 500 rds to avoid them. I also think one or two of my Ruger box magazines are wearing out, and I have tried cleaning them and retensioning the spring. The factory sights on the basic model (18.5" carbine with band) are somewhat tough to use with the tiny notch and hard to see gold bead. Also, the trigger is terrible, with about a 12lb break, and good luck getting the scope mount to stay tight and not wobble, unless you use loctite which Ruger specifically tells you not to do. Finally, while basic disassembly is very easy (though not as easy as an AR15 or the Ruger P-series pistols), if you choose to remove the bolt it can be fairly difficult to get it back in.
I added a promag recoil pad (about $6?) to my stock, adding 1" length of pull which makes a huge difference for my 6' frame, and added a Bell & Carlson extended mag release ($4) which is nice.
Ruger could improve the 10/22 about 10 times if they would just build in a scope mount rail and improve the trigger. The use of fiberoptic sights on the new "rifle" model is a big plus IMHO.
I also have a Walther G22 bullpup. The bullpup is really cool and it has some other nice features like a last shot bolt hold-open. Unfortunately stripping and cleaning is much worse than the 10/22, and you WILL lose one or two tiny springs when you take it apart - that being the bolt hold-open spring (which actually isn't really necessary, I left it out and gun works fine if held right side up) and the magazine safety spring. If you want a G22, CDNN Sports is clearing them out, just have your local FFL call up CDNN.
If I was buying another semiauto .22 right now I'd probably get either a Marlin or a Remington 597. But I say that without having owned either one.
I am looking to do more .22 shooting and actually was just about to buy a Savage Mark II FSS with the accutrigger. Does anyone have a Mark II? Any comments good/bad?