I am getting the most annoying issue - game freezing. It can be triggered in a certain area (like Weatherleah), it can be triggered when a hostile NPC (like OOO vampires) casts a spell on self.
Testing a new character through the same areas, no freezing. So most of this is either due to something that sneaked into an earlier save game (corruption), or just a size limitaiton on saves after which they would implode (or run into other problems).
What are the sizes of your save games? How many hours have you played those. It would be best if we got some numbers from the longest played save games to get a feel for if save game size limit is a real issue.
PS: Is the large save game caused due to OBSE mods? Like BEAR, that keeps track of a million armors and weapons?