For me, one of the saddest moments, was in my current TT game set in the Theban tribunal.
I was running the intro story, of how the magi came into possession of their covenant. At the climax of the story, a magus who had first enlisted the players to help him solve a mysterious disaster at his covenant and then appeared to die half way through, reveals that not only is he alive but he was the one who created the entire disaster to start with and had the ultimate goal of releasing all of the Titans from Tartarus.
There was a ritual involving a boy of around nine, who had be captured and chained for most of his life by these Titan freeing magi. The boy, who was a descendant of Poseidon, was to be sacrificed to free the giant Polybotes from under Nisyros. Once freed the giant would rip open the gates of the Titan's prison.
The characters managed to thwart the ritual and the plans of their traitorous magus, saving the life of this poor innocent child. They comforted him and unbound him and told the boy his life would be much better and they would see to it he would have a glorious life.
Then Polybotes began to awaken. The giant, who sleeps beneath the island, started to stir and grow agitated. It seems the ritual brought him to close to consciousness for him simply to return to slumber. The players attempted what they could to stop the giant, but this primordial magical being was beyond their powers.
It came down finally to a sacrifice. The boy whom they had just saved was the only blood powerful enough to be given to return the giant to his sleep. It was a long sad scene, where each magi came to terms with their choice. If they did not make a sufficient sacrifice, the giant would awaken, and while he could not free himself of Poseidon's chains, he could however rattle and thunder causing the entire island to erupt in a massive volcanic blast that would kill the thousands of people living on the island, and possibly kill many others along distant coasts, as the earthquakes and eruption would cause a tidal wave to crush the surrounding islands, including Rhodes, Crete, and possible the mainlands.
However killing the boy to satisfy Polybotes ended up being their choice. Some of them refused to speak with the boy, others try to make amends, and even others tried to rationalize or make the boy believe his sacrifice was heroic. In the end however, the boy kept saying, "I've been a slave of your people, treated like a animal, and now murdered. Whatever lies you try to tell me, I will still die. I will still die."
I am a often times morbid or depressing storyguide, but for some reason this story really choked me up... and the damn thing was my idea. My doing.
For me, it still rings as one of the toughest scenes I have dealt with. The salvation of the boy, just to moments later have to kill him anyway. Some bloody business that one was.