Molag Bal and Falmer are living under Markarth. Cannibals are defiling the dead in Namira's name. It's home to Peryte's latest border-hopping Epidemic. There's a Hagraven on every block. The Forsworn kill and pillage for freedom. The Reachmen are oppressed on their ancestral lands by the Nordic nobility. There're the Orc strongholds and there ties to Malacath if you want to count that (I don't). I'm pretty sure that I'm forgetting some stuff.
What in Oblivion are they putting in the Karth River? Was there some cataclysmic event to make this place so effed up?