How to route plexiglass?
A milling machine would certainly work. As you say, access might be an issue. One other way to address your issue comes to mind. Perhaps you can make a laminate. You are already going to laminate this with glass. Why not form a laminate with the glass on one side, solid plexiglass on the other and in between put pieces of plexiglass that have been cut using a saw? Draw the channels out on a piece of plexiglass that is as thick as you want your channels to be deep and then cut away the material where the channels will go. You could use a bandsaw, jigsaw or even a handheld jigsaw to make the cuts, although a bandsaw with a blade designed to cut plexiglass will likely give you the cleanest cut. Another advantage will be that no sanding and buffing will need to be done on the bottom of the channel as that is just the face of the solid plexiglass sheet. The sides will be exposed and thus easier to sand and buff into a smooth and transparent surface.