If it's acrylic it will be easy to drill. Yes a hole saw from home depot is fine just go slow and be patient, you may have to stop a few times and let the holesaw cool a bit. I would take the bulk head to the store with you to pick out the best fit.
I have never had a hole saw grab hard enough to crack the acrylic but if it grabs, you should stop and remove the holesaw out of the groove and start the drill and work your way back into it. Using a drill with a selectable clutch is a nice safety feature, set it low.
I also use blue painters tape to mark the hole location.
I also stop half way through and start drilling from the other side. This gives you a nice clean hole all the way through.