"Head home to see your family." Six words every player has waited to see since popping the disk in the machine.
The stranger mission "Who are You to Judge?" Though the ending is... odd, Jeb did get his sweetheart back, and for a horse, she seems to love him too. Particularly when compared with the other stranger missions, which tend to end in Nightmare Fuel or a Tear Jerker, this one is a welcome break. Then again, it says something about a game when one of the happiest endings you get is a guy being able to bang his horse.
For me, it was Landon Ricketts getting to pass away peacefully in his sleep. Anyone with a solid grasp of history knows that most historical gunslinging legends(Wild Bill Hickock, Billy the Kid, ect.) were usually brutally murdered. This includes John, who gets gunned down by an entire company of U.S. soldiers even after going through hell to see his family one more time. That Ricketts was able to avoid the fate of many other legends is Heartwarming, if rather bitterly.