Disclaimer: I have no idea how difficult the scripting on this idea would be.
Howland A town filled with disease-ridden PCs appeals to me.
Disease can be very difficult for the player that becomes diseased, but I see very little fear of diseased individuals in general. In a small community like Sanctuary, a sudden outbreak of disease could be a big deal. Plus, it would be super fun.
Would it be possible to have diseases, some or all of them, be contagious? Airborn or otherwise? I was thinking some sort of script that would check who was in the close vicinity of a diseased person, and make them roll a fortitude check to avoid catching the virus. An invisible aura of disease, perhaps? The idea of diseased members of the community having to avoid the rest of the residents until they recover sounds like great fun. Again, I know absolutely zero about scripting, and this may well be a nightmare or impossible from that perspective.