The moment when you reassemble Animatronic Goofy and he unlocks Ortensia's house. When you step inside, you can get her locket to give to Oswald, and in the background you see her rabbit children crying and looking up at her picture.
The ending of the comic story "There's a hole in the sky" where Oswald discovers that there is a way out of Wasteland via the eponymous hole, and almost reaches it — only for Yen Sid to discover the hole and patch it up, unintentionally trapping Oswald in Wasteland once more.
Admit it, you shed a tear when Oswald FINALLY gets his happy ending when Wasteland is restored to its former glory.
Many tears were shed during that sequence, especially in the first part where Oswald and Ortensia are finally reunited at last.
Also, if you watch "Oh, What a Knight" once you unlock it, you see how much of the short's humor value was derived from Oswald and Ortensia's obsessive love for each other. With that in mind, see what has become of the happy couple in the game....
The reason Oswald had animatronic Donald, Goofy, and Daisy built is because he knew he would never meet the real Donald, Goofy, and Daisy. NOW TELL ME THAT'S NOT TEAR JERKING!
To elaborate more, Oswald used them to relive the adventures Mickey Mouse had... But it never filled the void.
They bring up the idea that, despite his massive popularity, Mickey might someday be forgotten. Thoughts like that could turn someone into a nihilist.
The cutscene where Mickey first sees Oswald's altered version of the "Partners" statue with Walt and Oswald holding hands has made quite a few gamers tear up.
Even Mickey himself was moved when saw that statue, though that probably had more to do with his statue being replaced by Oswald's. This is even more powerful if you've seen the real statue.
It gets worse when you remember the dialogue during that sequence where Mickey asks Gus about the reason Oswald's suffering.
Mickey: "What happened?"
Gus: "Well....you happened."
(Mickey sighs sadly to himself.)
Heck, a Youtube user is feeling crappy by doing a evil run for our entertainment. Find it after the good finale in this list.
When the Clocktower gets destroyed by thinner and falls apart, some gamers teared up. Even Gus cries a bit.
But most bad things a good gamer does in a game causes them to feel regret.