WiiMotes have been connected to PCs and used with homemade sensor bars, though I don't think the guts would fit into a Zapper.
I have been throwing around ideas on this as well. What board will fit in a NES?
To help with placement of a mini-itx board in my own NESputer, I printed out the attached PDF and cut out the board (thick paper helps).
Since it's primary purpose will be to emulate old consoles, I think I'll go easy-mode and just fit a board, storage and power inside. Though with more modding it's possible to have a board, half-height video card, storage, and a slim-optical installed, but power would be external.