I've often wanted a well implemented disease system myself, I'm not sure how easy it would be to do. But I'd love to see something with a range from 'common' to 'incurable', and a range of effects that can impact your stats directly or how you're perceived in the world. Maybe you have something that's a bit too visible that can only be contracted through a nefarious deed... that should impact how you're viewed, you know?
It can be tricky to really do it right though, I'm not sure how you'd code to account for the variety that would make a disease system truly good. Still, I'd love to see them try it.