What is the best tool to use when cutting holes in new door panels for the door and window handles? How about the screw holes?

I use a NEW, SHARP hole saw from the back side and stop it before cutting through the vinyl. I then finish the hole with a rasor blade to make a clean cut of the upholstery. Screw holes are done the same way, from the back, and finsh with a rasor. If you drill from the front, you run the risk of snaging on the underpadding and making a big mess.
Hope this helps,
-Bill

Good post BBaker I'm just about to do the same thing. My game plan was to do the same thing (hole saw), but I was going to put tape on the vinyl side to help in case the hole saw goes through, as far as the small holes, maybe poke a small hole with pick awl from the front? just an idea. Maybe glue the vinyl around the hole before installing the door handle...also are you putting a plastic water shield behind the door for moisture protection?

I will put the paper type barrier back on that was under the door panel. I am not sure if that is the moisture panel that you are talking about. The paper on mine is pretty rough, but will be fine under the door panel.

I will poke the screw holes with an awl, and drill the larger holes for the door handles.

Yeah, Tar impregnated paper is the type of moisture barrier the general used. Reproduction shops also offer a plastic version if you prefer. For my door panel holes, I used a set of leather punches. They worked very nicely. The real secret is not to have any sharp corners. Rounded corners are much less likely to tear out or rip.

Installed mine today, got them from PUI, they had a cut out for the window crank, simple simon. As far as the bottem screws the pick awl worked great. Had to make my own hole in the cardboard for the lower jamb inside clip hole, the other three were there no idea why they left one off.