For larger holes, it's actually better to drill a small hole first, then use a template the size of the hole you need, then router out the remaining material.
That's the profesional way to drill acrylic. If you lived nearby, you could just borrow my drill bits.
If you do go the hole saw route, drill slowly, pour water on the hole, take breaks. Otherwise you may heat up the acrylic and make a real sloppy hole that you won't like.
BTW (shameless plug for MACO courses), I learned all of this in the MACO clcium reactor class and the protein skimmer class.
Len, if you want circles, then cknowlto's list is good enough, unless your cirles is larger than 2 inch in diameter. For complicated shape or large opening, Louey's router is the way to go.
I usually put a piece of scrape wood/acrylic on the underside so that if the bit got thru, it will be less likely to chip / crack the panel or make rough cut. The last 1/16 inch is most important.
I JUst finished putting a 2 3/8 hole in the back of my acrylic tank. I made a 2 inch hole with a hole saw and then expanded the hole with a dremmel. I was surprised how powerful the dremmel is. I did all this to a tank ful of animals. I just drained enough water out to not intefere with the hole . I put a cup on the inside to catch all the debris but some shavings got into the tank. Lucky thing they float and can easily be skimmed out.
If you plan on using a hole saw make sure hole saw bit has a guide in the middle or it is impossible to not have it dance around and scratch it all up. stopping evry 1/4 of the way thru will help reduce the heat .