Laser - I wouldn't use a spade bit for anything except ripping holes into lumber. They're like trying to do brain surgery, with a chainsaw.
Regular drill bits do fine. However, my favorite bit, for most thin panel work, is a step bit. It will do larger than standard bit size holes and adds a level of convienience, by having all the sizes chucked up at once. (A must have. IMHO)
As far as tips...With Lexan/plexiglass, leave the protective film on until you're done. Actually, I also use a wide masking tape and tape the whole piece first. Not only does it give me a surface that I can mark on, but it also helps to minimize splintering and "tear-outs". I always start a plastic project, with a new drill bit, too.
As far as general drilling tips:
1. SHARP DRILLS!!!
If you buy a cheap bit, you'll get a cheap hole. Replace or sharpen them, as they dull.
2. Don't force the feed rate. Let the drill do the cutting, not your biceps. (Or, you're back to #1.) Also, when cutting metal, a few drops of cutting fluid makes all the difference.
3. Use a center punch, to locate your centers. (If you're gonna guess, why bother marking it!)
3. Don't drill a big hole, in one step. (You'll never get it right.) Start with a smaller bit and drill out the center point first. Depending on the final diameter, you may need to step up a couple of times.
4. Make sure your piece is clamped down and stable. Nothing will break a bit and f#*k up a hole faster, than a piece that can move.
5. If you're going to do this alot, invest in a small drill press. (A must
if you're going to be tapping the holes.) They are very reasonably priced. All of the problems that the above tips address are greatly minimized, by using a drill press.
For holes that are too big for a bit, I'll use Greenlee knock-out punches or a scroll saw.
Hope that helps. Have fun.