Do you mouse with your left? If so, WASD is pretty awkward with your right, particularly in terms of reaching all the other surrounding keys. I wouldn't be able to comfortably hit the Space bar with my pinky, or the Shift key with my thumb while keeping my fingers on the movement keys.
If you're using your right hand on the keyboard, it's much more comfortable to set up a layout that somewhat mirrors the default keybinding. It doesn't have to be the numberpad, but I find it gives me the best layout of peripheral keys for all the typical functions found in a FPS-type game. I have a set-up that I like and I'm used to. There's no good reason that the numberpad keys have to be locked out to match the number hotkeys, and there's no reason for functions to be hardcoded to use E instead of remapping to whatever you set as the Activate key. It's poor and sloppy coding, and it's fairly trivial to change if you have access to the relevant file.