Largo's theme is an in-universe example in Chapter 2, while Guybrush is waiting for his mast to be repaired.
From Telltale (a Shout-Out to a fan video and the third game): "Oh, there's a monkey in my pocket,/he's attracting all my change,/his tail is a magnet,/and I think that he's got mange..."
Epileptic Trees: Tales is like an incomplete puzzle that invites fans to submit missing pieces: especially regarding the role of the Voodoo Lady in setting the story in motion, and her allegiance and motivation. Also begging to be explained is Elaine's seeming prescience (made even more puzzling as she is not in her right mind most of the game) — people even theorize that Elaine has voodoo-like powers.
Guybrush befriends Morgan and then gets betrayed by her and handed over to the Marquis De Singe on Flotsam Island for 30,000 pieces of silver... kind of like when Jesus befriended Judas Iscariot, who later betrayed him and handed him over to the chief priests for 30 pieces of silver.
In Chapter 4, Guybrush is brought to trial for charges, including that of spreading the Pox of LeChuck, and almost sentenced to death before LeChuck arrives to save him. In the Bible, Jesus was brought to trial before the Sanhedrin and before Pilate and Herod before being condemned to death with no one to help him, in order to fulfill the Biblical prophecy of long ago.
In the same chapter, Guybrush cures Elaine and everyone else across the Gulf of Melange of the Pox of LeChuck, and then gets betrayed by LeChuck and pierced by his Cutlass of Kaflu before dying; kind of like when Jesus was pierced by the nails of the cross and died to save humanity from all ills.
In Chapter 5, the map of the Crossroads is shaped like a cross where Christ was crucified. The map patterns are: Gateway = feet, Center = heart, Swordfight path = right hand, Treasure Hunt path = left hand, and Thieves' Den = head. Coincidence?
Arguable since it resembles more the veve/symbol of Papa Legba, who, like Galeb, is an important figure in Haitian Vodou who stood at the Crossroads and was responsible for allowing/denying communication between the land of the living and the afterlife, often portrayed as an old man with a walking staff, a pipe and an affinity for dogs, sound familiar? This makes it less of Christian symbolism and more a case of the people at Telltale Games actually doing the research.
In the same chapter, Guybrush makes his journey through the Crossroads, manages to unite himself in spirit with his body, and returns to destroy LeChuck once and for all through his trials and pains, before closing up the Crossroads with a sacrifice of his Shred of Life and using Elaine's ring as a part of the Crossroads exit spell to return to life and reunite with Elaine in the living world in his fully revived body. All of this makes a pattern to Jesus' descent into the netherworld and resurrection from the tomb to destroy death and Satan once and for all. Guess that's one more bit of faux symbolism added to this trope!
Moral Event Horizon: LeChuck trying to drown Guybrush, hanging him above a pit of acid, chasing him around with a voodoo doll, trapping him in a cursed theme park and stealing his wife was all in good fun. But LeChuck's running Guybrush through with his sword after pretending to be redeemed is something completely different.
Shipping: Some players think Guybrush should ditch Elaine for Morgan.
Special Effect Failure: In the scene in De Singe's lab in Chapter 2, De Singe and Morgan are quite blatantly standing in front of a flat image of the lab. Presumably this had to be done due to the filesize limit on the WiiWare release.
Squick: Guybrush gets creeped out wherever the Voodoo Lady's personal life is concerned. As the plot involves tracking down one of her ex-boyfriends, it happens quite a bit.
The ending of episode 4. Elaine and Guybrush's final exchange before he dies; obviously negated somewhat due to his resurrection at the end of the next episode.
Before that, there is also a scene in Chapter 4 when Guybrush is surprised to find Morgan LeFlay terribly wounded and holds her close as she tells him about the incident in the Marquis De Singe's laboratory, and after whispering out a warning to Guybrush (which he somehow misunderstands), she breathes her last; and he feels deeply grieved (though his Manly Tears may be invisible) as he pulls her sword from her not-bleeding body and has her hands enclose its hilt, tilts her head in a proper death pose and closes her eyes before getting up with an angry snarl of "De Singe!" The sad music doesn't help matters either.
While Guybrush has always been this to some extent, in this game it's taken up a notch.
Noogie. A Hollywood Nerd and probably the nicest member of De Cava's crew. All he wanted was a date with Morgan LeFlay... When the rest of the crew, and their captain, pull a Face–Heel Turn at the end of their chapter, he's the only one who didn't approve... and an offhand (and missable) line implies they murdered him offscreen for it! A suspicion that would be proven true in Chapter 5.
Jerkass Woobie: Hemlock McGee's life keeps getting worse and worse. He only partly seems to deserve it.