House, M.D. on the Nintendo DS seems to be entirely driven by .xml files, uses normal .png files for textures, and normal .wav for its sounds. If you were so inclined, you could probably easily put together a ROM hack that adds new cases or even make a total conversion.

I think the minigame logic is essentially hardcoded, but the layout XML seems to use some sort of command system that seems to trigger animations and draw polygons and what not but might do other stuff too. Maybe you could add new minigames or something if you could figure out how this worked

I don't know what compelled me to take a look at this