This is based on opinion. Please don't list it on a work's trope example list.
Tear Jerker / South Park: The Stick of Truth
When you kill Nazi Zombie Chef, after Clyde burns him when he comes to his senses.
Defeat his "Hello Children" attack, and he'll spend a whole turn with a Thousand-Yard Stare and a horrified expression.
In a way, Butters and all of the places he mentioned he got beat up or bullied in some shape or form and just says it so casually.
During the boss fight against Butters if you choose to side with Kyle's elves, delivering the final blow has him depressingly say that nobody likes him.
On top of that, the description for Butters' hammer states: "You struck down the first friend you ever made in South Park. Then again, it was Butters." That doesn't exactly help much, depending on if you found it funny or not.
Butters even cries when you defeat him. It's heartbreaking.
Especially after he takes his already adorable Apologetic Attacker attitude to the next level by assuring you throughout the fight that no matter what happens, it's just a game and you're still friends out of it.
Someone created a parody of this scene and Ryuuko's brainwashing from Kill la Kill. He might have actually made it worse.
Similarly, when you defeat Kyle, he either says "Bury me at my base", or, like Butters, sob pitifully.
During the assault on Clyde's castle, one of his henchmen beats up Ike when he tries to lower a ladder, making Ike cry. Not only is this kid WAY bigger than Ike, he's bigger than all of the other kids, he looks like one of the sixth graders for gods sake! Which makes it extra satisfying to blow him up with Dragonshout.
Tweek gets a little too into the game during the battle at the school. Witnessing several of his friends "dying" leaves him with a Thousand-Yard Stare and tears in his eyes.
The fact that you're forced to fight someone whom you thought was your friend and kill them multiple times is a tearjerker in and of itself.