Practically every scene with Glottis after the first Year is heartwarming, but when Manny finds out that Glottis survived going over the edge of the world, it's really sweet.
Manny naming his boat after Lola.
Chepito's departure into the Tunnel singing his Theme Song "This Little Light O' Mine".
Also, his thanking Manny for setting him straight (he'd been walking in circles for years) - without Manny, he'd have never gone on to his final reward.
At the beginning of the fourth act, Manny has traveled all the way to the Tunnel into the Ninth Underworld, which has been his goal the entire game and his only motivation at the start, and is now able to walk into it, leave everything behind and finally achieving his well-deserved rest. But he doesn't. He feels too much responsibility for all the poor people he's traveled with that he's determined to help them enter it first, even if he risks losing the opportunity himself.
Everyone who had been slaves to Domino on the train waving at Manny and Meche at the end.