For a 2D space exploration with a combat system, would you rather point with the mouse or at the direction you're moving

I want something you can just sit down and meditate while you act, combat and explore, so i want very low body resistance, which I feel like the mouse could cause.

Using WASD for firing and Arrow for direction seems way better, but that would limit the aiming pottential.

Any Ideas?

Think about The Binding of Isaac, Magic Survival (a bullet hell kinda)
I think the aiming system of LoL is cool, but it's too high skill and I dislike using the mouse too much. (Although using an ergonomic side-mouse could solve that issue).