In the episode "First Class Feline," Jon, Odie, and Nermal think Garfield has accidentally mailed himself to Abu Dhabi. Jon is desperately trying to stop the plane but doesn't make it in time. As the plane is taking off Jon yells out "My cat!" It even features the same music from the specials that plays when something depressing happens.
Lenore moving away in "Stark Raven Mad".
The poison apple scene from the episode "Snow Wade and the 77 Dwarves", because it was Orson who caused them to not be able to rescue Wade.
It was also sad because Orson just went ahead and put Wade in danger, thinking it all as just a story(even though he should know by now that his imagination comes to life) and didn't even have any regrets about it.What the Hell, Hero?, indeed.
Out of all the characters, Roy was the only one (who was taking this seriously near the end of part two) who seemed alarmed/upset that Wade could really be hurt/dead when Wade wouldn't seem to wake up, after Roy kissed him while the others just looked on curiously.
Wade Duck on the verge of tears in the episode Quack To The Future after Orson yells at him. He definitely becomes a Woobie in that episode