I never like WASD setups (even where it's not used for movement). I can't comfortably keep fingers on all four WASD keys at once, meaning that I have to shift at least one finger up and down, and when that happens, I always lose track of where my fingers are on the keyboard and I end up hitting the wrong buttons to make my character do stuff. I hate it!
Where it's necessary to use four keys for movement plus at least four other keys for actions, I use the Arrow keys for movement (with no other buttons nearby, it's easy to keep my fingers in the right place), and I tend to use ASDF or ZXCV (in general I find it more comfortable to keep my fingers low on the keyboard), and I use Spacebar (which is nice and big) for the most crucial actions like Jump or Attack. If the game requires movement keys, action keys, AND a mouse, then I find the game to be completely unplayable unless I can hook up my gamepad and play using that.
However, when designing games, I try really hard to limit the number of buttons that will be needed. In timeblazer, for instance, all 28 action games can be played using only the Arrow keys and the Spacebar. (Combat adds one extra button, Shift, but it's turn-based so there's less need for controls to feel completely second-nature.) There are a few other functions like pausing the game or bringing up the instructions overlay during play that require other keys, but none are essential to normal play. The goal is to keep the player's focus entirely on the onscreen action, rather than losing their immersion by forcing them to think about what buttons they are hitting.
