I have a graphite G4. Your main problem will come from your heatsink. The RAM is located on the logic board in such a way that it is actually above the optical drive when closed so no worries there. The heat sink will provide only a minor headache if you are serious about this mod. I have a OWC G4 700 upgrade and it comes with an L shaped heat sink with a fan located on the side of the L that is not on the processor.

Even with this setup, a 5.25 drive would touch the heatsink. You will have to resort to a custom heat sink and no doubt have a fan attached to it as well. Its very possible, just a bit more difficult that I originally anticipated.