The latest method I've been happy with is to use two sheets of a lighter weight plexiglass.
I make a paper print of the panel and samwich it between the two sheets.
If, or rather, when a change is needed I can print a new sheet and reassemble the panel with the new sheet. Most of the time it is due to adding switches and track so that just means drilling another hole or two.
As for drilling plexiglass, I've had more luck when using a rather dull bit which runs hot. This way I'm melting as much as cutting. But I'm still not consistant with this. So I'm hoping one of the other posts has better ideas.