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Tear Jerker: Ōkami
The whole endgame of Ōkami, from Issun's departure, to the ghosts of the Celestials telling how they died, to Waka's tale, to Ammy's Hope Spot halfway through the final boss battle.
Tobi's death. The little guy was helping you all along and then gives his life up to help Ammy reach the boss. He even left a small flower where he faded. Poor Scrap.
Which makes it all the worse when you realize his final words are how he wishes he could offer you a flower in congratulation and that this is the first time he's enjoyed himself so much. He then proceeds to turn himself into a flower and, even though all enemies do that when they die in this game, it hits home that much harder because his final act becomes the fulfillment of his final desire.
Just Waka's tale in general. Although he does not outright state it, he hints he is the last of the Moon Tribe. He also was the reason that Nippon has demons in the first place. His whole Trickster Archetype is based on the fact that he doesn't want to let anyone get hurt. And when he saves Ammy from Yami at the apparent loss of his own life...
Well, he isn't really the last, there's also Kaguya.
After your adventures inside the Dragon Palace, the dragon orb shows you a vision of the REAL Rao being attacked by the demon Ninetails. Cue epic music as Issun rushes you to where the vision had shown you. Once there, the ghost of the real Rao leads you to a secret tunnel. So when you go into the secret tunnel, you find a decayed corpse. Guess whose it is. This is one Player Punch guaranteed to leave you winded.
You see? Nobody remembers Queen Himiko, not even the people in the game itself. Both her and Ammy knew that she had to die for her plan to work from the very beginning yet none of them mentioned it, her sacrifice is quite tear jerking. The way she manages to linger on in this world for just one more moment in order to finally determine the location of Oni Island for this one sunset was also rather sad. The saddest part of this is the fact that after her death, the number of people that mention her at all can be counted with one hand, meaning that her sacrifice was never known by her people.
Actually, a fairly large number of people in the Aristocratic Quarter talk about her death and how they need to keep the peace she saved for them. The truly sad thing is that the Emperor never talks about her.
Even before that, her entire situation was incredibly poignant. She did all that she could by praying constantly, but until Amaterasu happened upon Sei-an, it was doing absolutely nothing. Her people were crying to her out of anger and desperation and she could do almost nothing to help.
Kaguya going back to the moon.
Issun imploring the people of Nippon to pray for Amaterasu's safety and give her their strength in the final battle never fails to turn my waterworks on.
Going back in time and eventually watching as Shiranui dies.
"Reset (Thank You)", which plays during Ammy's Darkest Hour.
The song becomes even more poignant when you remember that this is one of the last games Clover made before being shut down.
The one part where you are eaten by a dragon, and you tamper its insides so much that you end up killing it by accident, and it's not even in the least bit played for laughs or awesomeness. You just feel bad for doing it.
The song that plays as it falls into the depths really doesn't help. It gives you the feeling that you just destroyed something beautiful and majestic
And then you go tell Queen Otohime, where Issun breaks the news in the worst possible way.
The music that plays when you're in a cursed area, particularly Shinshu Field when you hear it for the first time. That flute...