I didn't normally play games on the PC, and if I did, I used my arrow keys. But then I got into the PC version of Team Fortress 2.
At first it was weird playing the game through using the WASD keys. But then I realized that the set up really isn't that different from a console controller. You use the movement keys with your left hand, and you perform actions on the mouse, such as firing your weapon, with your right hand.
Once I've acquired that mind set, I found the WASD keys to be very comfortable.