The latest horizon for my projects is to put custom PCB's into nice-looking enclosures from polycase.com. This involves a display, buttons, power jack, A/V jacks, Ethernet jack, etc. Getting the connectors on the PCB to line up with holes in the enclosures, and MAKING the cut-outs in the enclosures is turning out to be tricky. (Unless it's just a simple hole in which case I can use the drill press.)
Does anyone have any good references to how-to guides or just general advice on doing this?
Start with getting the board mounted in the case & keeping components cleared from the mounting holes, and sizing the board to fit in the enclosure.
Then make everything you want to mount to the enclosure have flexible wire connections down to the board.
Get some small files to work the plastic after you drill the holes.
Adding to what CrossRoads said, keep in mind any factors that might predetermine external connector, control or display placement and then specify each component to manufacturer and part number. You will need the exact specifications of each component that needs a hole or aperture in the outer cabinet and their spacing requirements from the circuit board. Don't work forwards from the finished PCB, work back from what you need the final product to look and function like. You need to consider things like handling, useability and attachment of external connections as well as cosmetics.
Making the apertures might be done with punches, depending on the material the cases are made of. Polypropylene, polyethylene, polycarbonate, ABS and metal can be punched easily. Otherwise, you might be into cnc milling or even cast or molded in knock-outs for more brittle materials like polystyrene, which sound like they are well beyond what you want to do.
and if you need batteries, make sure it has a battery compartment to save taking the whole thing to pieces
ask me how I found that out!
Be really precise in designing the boards and sizing the case. Then use a CNC mill to cut holes in the case. If you measure right and compensate for cutting kerf, washer thickness, etc, it will Just Work (tm.)
Check your local maker/hacker space for access to a mill/router/shopbot.
If you do it for a lot of devices, look into vacuum forming your own case parts. Again, a maker space or fablab can probably help.
Thanks for the tips, everyone! A CNC mill, that sounds like just the ticket, I'll have to see if I can round one up. I used the drill press and a chisel this weekend for the ugliest-looking display cut-out ever. The tip of having a few files is an excellent one, maybe even a tiny orbital sander?
What software is optimal for creating the files for milling? Polycase will do milling, though they seem to want AutoCAD files, and I'm not quite up to spending for $1200 for AutoCAD LT 
if you use EAGLE there is a plug in for generating gCode
that is the lingua franca for CNC
The Eagle code generates isolation milling to make pcbs, not cases.
You can actually write gcode manually for cutting a few straight holes and drills pretty easily.
As for software, I use inkscape (free) or 3dsMax (expensive, may have free home or trial edition) and import into VCarve Pro. My maker space (TechShop) has licenses.
There is a program im just learning to use called yenka. www.yenka.com it lets you design a schematic and then you can choose a type of board, including ones mounted in cases so you can see where the holes need to be... its a mighty program that seems to simulate allsorts of physics things...
I made a lot of progress on my first enclosed system yesterday, thanks again for all the tips. The key for me was going with two pcb's, one for the top panel to connect the display, buttons, led's and other stuff that comprises the interface, and a separate panel for the main board, connected by a ribbon cable. Then, using bare prototype board to physically simulate the PCB and drilling holes so I could mount it under the top of the enclosure. From there, everything fell into place. Now I (almost) have a fully-built unit with no actual electronic connections. Yay.
Next thing I'm going to try is drawing to the milling layer in Eagle, and spitting that out as an EPS during the CAM job. With an EPS I can do a laser-cut acrylic at Metrix Create Space. That'll serve as a prototype of the panels, so I can see that everything is lined up nicely with CAD-specified cuts. Then I'll have to figure out where in Seattle I can do the actual milling of the case. (Metrix won't laser cut ABS).
Yenka looks super cool, but not ready to spend the $$ until exhausting all free options.
It is free.
It used to be called crocodile clips.
Just wanted to say thanks for the tips that folks shared on this thread. I finally got my unit completely built.
Details here: The Camera Machine – Multicam Prototype | maniacbug
[[/center]
P/S This picture is actually a self-portrait, taken WITH the unit in the photo 
](The Camera Machine - Multicam V1 | The Camera Machine - Mult… | Flickr)
That looks pretty rugged and well put together. Nice job!