NeX has actualy been discussing this very idea with me. Cool to see someone do it. Here's some advice:
Add ground planes. Ground planes help reduce interference and potential soft errors. The area around the crystal makes me worried, for example. Also make any power lanes slightly wider.
The display board has little springy contacts. These are ground connections, and you should ideally reserve an area that is not covered by silkscreen to allow them to connect.
The GBC cartridge socket has the ground pin moved one unit moved forward. This mean that the ground pin is the first thing that makes contact when inserting a cartridge, and the last thing that disconnects when pulling it out. This is good because it prevents latchup. Add another ground hole, so people can use a GBC socket if they so wish. (BTW, I know a couple of guys who have desoldered GB sockets of different kinds that I can hook you up with.)
Hint: If needed, you can internally rearrange any of the address pins that are in use on the internal RAM chips, and any of the data pins as well, if it helps the routing. As long as you can write a byte to a position, and get back the same byte from the same position, all is well. (This is not true for the cart slot, of course, where things already have their place.)
Hint: If it helps, you can rotate chips 45 degrees. Not only will the board still come out just fine, but most fab houses can solder components at non-90 degree angles as well, if you'd ever go that route. (Down to 5 degree increments or so, I think.)
You might be able to move the components on the headphone daughterboard to the main board, for those who want minimize the daughterboard. (NeX ) The way I'd do it is to put a cuttable trace which bypasses those components, that you leave untouched if you don't want to connect those components to the main board.
Bypass caps are good - rather a couple uF too much than the opposite. Throw in a couple of ceramics as well, for good measure. (Regular common wisdom in electronics.)
A designated area with two extra holes for gnd and two extra holes for +5V wouldn't be wrong. Might come in handy.
Lastly, make sure that everything will fit, and no components will stick out too much etc.
Also, I have an idea for doubling the amount of available RAM, which would be possible if you could find a suitable 16 kByte chip, or fit two 8 kBytes on there. That would be very much of a "just because I can" type thing, and wouldn't actually be that useful, since no software supports it.
Also, if you're in for a challenge, you may want to try to redesign the power board, perhaps using MOSFETs for better speed and efficiency.
I'm sure I can come up with more things later, but I need to sleep. Would love to try this board out at some point.