This is based on opinion. Please don't list it on a work's trope example list.
Tear Jerker / Jade Empire
Kindly Yushan burying the bones of the children who died in the orphanage in the flooding of Old Tien's Landing.
When Aishi the Mournful Blade asks you to Mercy Kill her because she has nothing to live for and she's too consumed by her guilt. And you'll be forced to do that because she attacks you even if you refuse to kill her. What's worse, at first she asks that you give her an honorable death... then stops and says she does't have any honor left, so just kill her and be done with it. Soft-hearted gamers will cry buckets, especially after meeting her ghost father.
Wild Flower is the personification of a tearjerker moment. She is a poor girl who died during the flood in Tien's Landing and who now has the souls of two rival spirits dwelling inside her and warring over possession of her body. Her innocent struggle with them and her painfully sad fear of the bad spirit could make a statue cry.
There is a mission wherein a doctor is trying to find a fresh corpse in a graveyard to replace his daughter's dying organs with. The player character finds an Undead by the name of Ji Xin who preserved his corpse out of fear of the afterlife because he knew he was fated for damnation due to all his sins. The player can simply kill him for his organs, but if you persuade him, he gives this heart wrenching line, "For a little girl? Yes, very well. If Damnation is my fate, at least let it be worth something in the end."
An alternate path is to seek out Doctor An at the Arena, and she will perform the necessary surgery, and the girl's father will give up his own liver, and his life.
Miss Chan's fate in the Necropolis quest. Not only did she die in childbirth, but her baby died along with her, and she's understandably unable to accept that fact.
You can spiritually enslave Death's Hand. When your party objects, you can spiritually enslave them. And you can steal the power of the Water Dragon. You will never feel so bad for doing anything else in a videogame.