I used a hole saw to make 2 X 4" holes for my fans. See reply 54 in my build thread here:
http://forum.arcadecontrols.com/index.php?topic=110471.40I think it turned out really well. Hole saws are not cheap. I paid ~$20 USD for a 4". If you go up to 4 1/2" it's like ~$30 USD. The cheaper core saws only have threads in them. You then have to buy a drill bit adapter that screws into this. It's more upfront cost, but if you need to buy another core saw later on, it's cheaper in the long run. What's nice about this setup is the drill bit helps keep is lined up in the hole while it cuts. If you go this route:
1) Drill at the highest speed setting you can.
2) Let the saw "do the work", don't push on it too hard.
3) Make sure you hold it perpendicular to the surface being cut. (Brace yourself nice and solid.)