Get yourself a couple of 2x8 chunks of wood. Hole saw one of them first, put the other on the back side, C clamp them in a fashion that doesn't bend the fender all up. The side that is already sawed will act as a real nice guide. I do this when I need to make oval holes and it works really well. I will also serve as an easy way to make sure the hole ends up where you want it. You can use this method at an angle also if you need to.
And yeah.... out the top would be my choice also!