I just rewatched The Fires of Pompeii and realized that we've been through all of this before. In that story, the Doctor has to sacrifice 30,000 innocent people in order to save the world. It's set up as an explicit either/or decision.
It sounds like if the common Time War theory is correct, that it's this basic scenario but amped up to a universal scale! The Doctor didn't seem to troubled over this decision, a bit, but not nearly as much as Donna.