What about adding some "mutations", "additional perks", "conditioning stats"... I dont really know how to call it; lets use as an example a very well known series with five games and an MMO; In this games, you could build your character in certain ways depending on how you distribute your skill points ending up in many different gameplays, maybe you could be a swordsman who uses magic, an almost invisible and lethal archer, or a berserker barehanded.
But, in certain moments of the game you could be infected with, for example, vampirism or licantropy. In this cases you would gain some habilities, some buffs and, of course, some debuffs. I guess it would be hard to add it to the game in early stages because it would complicate the balance between classes. Nevertheless, it could give an extra in aspects of uniqueness in builds, comunities of roleplay, and factions ingame.
As comented in other posts maybe a well known pirate could be cursed making them phantasmagoric, an assasin could be willing to live in the shadows with a comunnity of vampires, a paladin could become a saint gaining power against dark forces, maybe that priest wants to be the one in charge of doing exorcists to those unholy creatures. I dont know, there could be plenty of combinations. (It would be cool to see some saint necromancer or a vampiric paladin...)
Just leaving an idea over here. ^^