I used my dremmel. I cut a majority of the plastic out with the abrasive wheel, then used a straight mill type bit that cuts with it's sides to finish off the hole. Then I smoothed it out even more using a small piece (3" x 3") of 100 grit sandpaper curled around 2 fingers.
To mark it, I used a mini cd (80mm) and a scribe (any sharp point) to scratch the outline into the plastic. This line cannot be rubbed off by accident when your handling the plexi, and is more accurate to cut to than a marker line.
Using the double thick plexi allowed me to cut, dremmel and sand off much of the fan's frame to press fit it into the hole with no glue....looks pretty darned good if I do say so myself.