I plan to save right after setting up at least two possible end-games (NCR and House), if not three (Yes-Man) with my current character, so I can play through an end-game or two, and then go back to that save to play out any interesting side-quests that are left, leaving the end-game unresolved.
I'm currently at Level 22 on Normal on my first run through, and given my rate of leveling up, I think I should be starting a sequence pretty soon. Can I wait until about Level 26, or would that be too late?