Secretly Depressed Don Cheadle is in of itself an amazing thing.
Being an actor no one remembers the name of, or remembers in any movie after at least a month, despite being in almost every movie in existence is depressing.

His smile can sometimes not seem sincere, or real, as if he's putting it on, while secretly cover up his internal anger or sadness.
While It's exaggerated. it can sometimes be used in hilarious situations.

His first name "Don" is also easily used, or rhymed to a pun, therefore making it easy to create a punchline in the joke, as the source exemplifies.

An good example of this can be seen on his Wikipedia Page, as the first picture of him.
While i have no idea why they chose this, it wasn't a bad idea.