After completing the pilot hole, I took my trusty hole saw and went to work.  It is very important to be careful and slowly make the cut using little pressure.  You want the hole saw to do the cutting for you.  Otherwise you could crack or melt the acrylic. 

Considering at this stage that would have meant ordering a new panel and breaking down pretty much all the work that I had done up to this point, I wasn't about to let that happen.

At this point I had pretty much only grazed the surface.

A little further in.

Once again I must apologize for the lack of pictures.  I remember taking photos of the finished hole, but I seem to have misplaced them.  At any rate, after drilling the hole, I used a 80mm fan grill to figure out where to drill the holes.  This is the final result:

Now that that was complete, it was time to move on to mounting the final motherboard and power supply.