Ass Pull: Using Sunrise on Otohime causes her to transform into the Water Dragon, albeit only temporarily.
Base-Breaking Character: Manpuku. You either think he's one of the best partners due to his strong moral values, him trying to save his mother even before you meet him, and having a few awesome moments. Or you think he's the worst for being introduced right before one of the last dungeons, having inappropriate comedic moments, and having a disappointing power (the ability to travel across ice spikes, an ability that Kurow could do better, and giving a fire source).
Fanon Discontinuity: While many agree that it is a good game, some choose to ignore it as a sequel to Okami thanks to the time traveling shenanigans that take place halfway through the game that start messing around with the events of the previous game. One of the most infamous examples people bring up in regards to this is reducing Susano's Moment of Awesome and Character Development in the original game by showing he was scared shitless at the thought of fighting Orochi, and was about to run away like a coward before Chibi forced him into confronting him, regardless if it meant his loved one would die as a result.
When you're told that everything you've done the entire game has been helping Akuro, even if you delayed the inevitable by slaying Orochi 100 years ago.
There are three others, as well: Seeing how the Goryeo sank (which is the sunken ship from the first game), seeing Shiranui die onscreen (with all the villagers and his grandson sobbing), and the Granddady of them all in possibly both Okami and Okamiden, Kurow's fate and how he sacrifices himself to kill Akuro, with Chibi and all your other human partners absolutely bawling as they try to convince him that even though he was a living doll clone of Waka, he was still a different individual. Cue the crying when "Everything Must End" plays as Kurow's life slips away from his body.
Ink only regenerates in Easy Mode; for those looking to challenge themselves in Hard Mode, it leads to frustrating moments where trying to solve puzzles leads to Chibi getting nerfed. To compensate, enemies drop ink pots far more frequently than they did in the first game.
There's only one save file. After finishing the game, you'll either have to play the New Game + or erase your data.
Unlike in Okami, "important" collectibles (those required for 100% completion) such as Fetch Quest items and the Issun Masterpieces become Permanently Missable Content if you don't collect them before their respective areas get locked off. This leads to a lot of frustrating Guide Dang It!, especially since this design decision was completely avoided in the previous game.
That One Attack: Akuro's ultimate attack during his first form, where he charges a laser, while attacking you his giant hands. What makes this difficult is that if his hands grab you, they will likely not let you go until he fires his attack, which not only take away half your health but also heals him. This means that any damage you've dealt will be fully healed if he has more than 50% of his health remaining.
That One Boss: King Fury. If you haven't perfected power slash by this point, he is probably one of the hardest bosses in the game besides the final bosses.
That One Level: If you get trapped behind in the underwater sidescroll just once, it's an instant game over.
Tough Act to Follow: As a sequel to the critically acclaimed Ōkami, it was inevitably gonna have a hard time even before release. In the end, it's seen as a good game in its own right, but nowhere near the level of the original. Not having any of the original developers for the previous game on the team would have something to do with it.
Visual Effects of Awesome: Despite having none of Okami's original developers, the team did a fantastic job of recreating its art direction on the DS's low-grade hardware. The Guardian Sapling scenes in particular have lost minimal splendor in the transition.