I'm currently trying to make my way through the "Don't Fear The Reaper" secret ending, and it's quite a challenge on hard difficulty. Probably the hardest challenge in the entire game. Well, that one particular character that you have to fight as you make your way to Mikoshi in the bowels of Arasaka Tower. HP is reduced, and reduces by so many percent every 45 seconds or so. Health items only work up to that reduced rate, or not at all if you are on death's door. And that character can easily one-hit you. No saves during the mission either - although it auto-saves at the point you meet AS so you don't have to run the entire mission from the start.