I've never had any unrecoverable glitch.
I use a mod that auto-saves the game every 5 minutes, plus I always make a new save before I do anything important, so if anything goes wrong, I always have a save to go back to. Even with that though, I very rarely have to reload. I don't use exploits and I don't try to do things out of order, and those seem to be the primary causes of glitches.
So the worst I have are a few somewhat predictable CTDs. I try not to save at the Waterfront Shack, since I've found that starting the game up then trying to go out that door often results in a CTD. I also get occasional CTDs coming up the path from the sewer exit to the bridge between the prison and the market district. There's a point at the top, coming around the corner toward the bridge, where the game tries to load something and if there are too many other things going on, it'll CTD.
And that's about it, really....
Sorry.