Afro Samurai. Specifically, the Kuma boss fight.
Every boss had a trick or two you needed to learn to beat it. Kuma had a couple. First, he blocked/dodged all attacks most of the time unless he was in the middle of an animation. He had a pretty strong moveset that his AI would often abuse for cheap hits; you could avoid the cheapest using a focus backflip, a maneuver you literally never ever had any need for anywhere else. But the worst part was that you couldn't use the same move combo more than once, or he'd start blocking/dodging the latter hits or autocountering you in the middle of your attacks. Use the same set of moves even twice in a row, and not only would he take no damage but he'd probably autocounter you for massive damage. Fortunately there were hundreds of combos to choose from and you could reuse the same one a few times... but there wasn't a lot of difference between any of the combos, so there was no real reason to not spam the same attacks over and over in any other fight.
It took me literally three days to recognize that this was why he was so hard to beat. It's not immediately obvious, because he goes through multiple "forms" over the course of the fight and he takes a long time to kill. I thought he just really liked blocking attacks near the end of the fight.
Also, another fight I had trouble with was the first Metal Gear Rising boss, since it expects you to know how to parry (the only method of blocking in the game). I wasn't used to the Japanese convention of special attacks and maneuvers being performed through a combination of thumbstick input and button presses (you see this in fighting games like the classic QCF input for Ryu's fireball), and MGR never made how to parry clear. In MGR, you had to be standing still, and then press forward and attack simultaneously during an enemies attack animation to execute a parry. You couldn't parry if an enemy wasn't attacking you, and couldn't parry if the thumbstick wasn't in a neutral position to start (e.g. you were moving). With expert timing you'd do a more powerful version that stuns the enemy and automatically counterattacked, and this became a potent skill throughout the game. But since there's no other method of blocking attacks, and the boss has attacks that effectively long on to you, you needed to at least know how to parry quite well by the first boss.
Last one: The first Dark Souls boss
I challenged my cousin to beat it and it took her 7 hours over two days. Nuff said.