shouldnt be too hard, unless you are laying out graphics that are really sensitive to location..for instance arrows or something around your joystick holes...if they arent in exactly the right spot, it could look stupid.
as long as that isnt an issue, it should be easy. you can use a razor blade to cut the artwork around the holes, just take your time. as for the plexi, clamp it to the wood and use a flush trim router bit to cut the holes, it works great.