Originally Posted by Nevander
Make sure you keep two or more saves this time. One at the previous level, one at the start of your current level, then one for current level progress. Then replace then as you go along.
I cannot support this enough!
There's another thread regarding the ladder glitches. It happened to me and was forever stuck in a room. Reloading saves did nothing as once the level is loaded, nothing is going to change. You need to start the level over and I was like 4 levels back (thankfully past Hell so they were short).
I kept a save right before I activated end level switches and always kept 3 levels worth of saves. This is just my collectibles run so not as bad as Nightmare, but still.