Most recent: cutting off Kalameet's tail in Dark Souls to get the Obsidian Greatsword. Most of the time it's airborne and out of reach, so one has to trigger certain attacks from him in order to actually hit the tail. Not to mention it took around eight hits to do so. Looking back on it now, it's probably not all that difficult, but at the time it was.
On the topic of Dark Souls, defeating Ornstein & Smough the first time was a major accomplishment for me. I had a lot of difficulty with that boss fight, and it took me around twenty tries before giving up and taking a break. I went back to playing DaS later, but I made a new save file instead. Why? Because I felt that I didn't have a good grasp on the game just yet. On this save, I decided to play through the game by practicing rolling and avoiding damage, rather than constantly blocking with a shield. By the time I got to Pikachu & Snorlax, it was a breeze. It just clicked then, and only took me two or three tries to succeed.