Fridge Brilliance: When LeChuck gets his voodoo form back, he goes back to having his original voice actor, Earl Boen, and, from then on, starts to make smarter and more dangerous moves. Basically, the true LeChuck is back.
It's not huge, but I noticed Guybrush walks differently when he's on a ship. He's got sea legs!
In Chapter 1, when you ask Nipperkin about Morgan Le Flay, he will tell you that none of the stories he heard add up, each pirate describing a different man, leading him to believe that someone's trying to hide something. Cue the reveal that Morgan LeFlay is actually a woman, and suddenly all the different stories make sense : none of the pirates would admit to have been beaten and captured by a woman, so each one made up a different description of the dreaded pirate hunter!
The first time you knock on De Singe's door, you can hear a man screaming, "OHHH HO HO HO! MY NOSE!" There is a nose-shaped pot next to the door.
Actually, when you try to knock on the door for the first time, the flowerpot falls off and Guybrush has to pick it up. This may or may not have been Fridge Horror.
In the Chapter 2 intro, the Voodoo Lady is seen reading Guybrush's future and predicting his death. In Chapter 3, you use these tarot cards to curse De Singe. She wasn't reading Guybrush's future - she was cursing him!
She also sends him to find La Esponja Grande, which gave LeChuck the power and caused Guybrush's death.