Fallout 4 best moment for me was finding the vault tech rep in the good neighbor hotel. That bit was just brilliant! Yao is a close second though...
Many of the companion reactions to the "Treasure" in Jamaica Plains are funny.
The "Burning Mattress", "Sandwich" and "Sound Effects Victim" stories that raiders share with each other are quite funny. (The last one just has to be a call-out to the Larvell Jones character in the Police Academy movies.)
Just about every thing KL-E-0 says is humorous.
Curie is fun to torture when you first meet her in Vault 81. She has been locked in that room with nothing to do for a century awaiting authorization to leave and she really, really, really, really is ready to get out. If you play dumb and keep insisting you don't have the authority to release her, she will get more and more desperate as the conversation continues. Eventually, she will get so desperate that she will open the door without authorization.