You might also want to check out Speedplay pedals, either their X or Zero models. They have a lot more "float" so they seem to be a little more forgiving on your knees on longer rides.
But if you're interested in SPDs, Specialized makes a shoe with a recessed area for the cleat, so the shoes are more comfortable for normal walking.
I've used clipless pedals for about a year now and haven't had any problems so far (knock on wood). I started out with SPDs, and had a little trouble getting the cleats aligned. The first few times I rode with them, my knees bothered me afterwards. A neighbor had been using the Speedplay X series and recommended them highly. I switched over to the Speedplay Zero series a few months ago, and like them very much.
My wife hasn't been so lucky. She has a Specialized Sequoia Elite, and tried the SPDs when she got the bike. In the first few weeks, she fell several times -- always at low speeds. One day she fell while waiting to turn at a traffic light and realized if a car had been coming she could have been hit. At that point, she gave up and went back to platform pedals. I recommended that she should get familiar with her bike first, then try the pedals, but what can you do, right?