Kinda depends on what hand you're using your mouse with as well I would think... I mean, I find it difficult to cram both of my hands into the area where the arrows and mouse are on my keyboard tray, but it's easy for me to sit with WSAD and the mouse.
On the other hand, if you use your mouse with your left hand, I can see WSAD and the mouse being as uncomfortable as arrows and the mouse are for me...
Still kinda depends on the game itself though. If all that's happening is moving, and the game supports hot-seat 2 player gaming, I'll use the arrows and mouse so a buddy can use the rest of the keyboard. If the game requires me to hit other stuff besides just moving (the easiest 2 I can come up with are UT2004 and BF2), WSAD all the way.