Even though Deadpool is damaged by Ghost Rider's Penance Stare due to gameplay mechanics, in the comics all he saw was a "highlight" reel (e.g. what led to him becoming what he was) and changed Ghost Rider back into Johnny Blaze.

When Deadpool is first in your party and goes up against Spider-Man, he says, "Gonna rough you up like a Broadway musical." This is a reference to the Spider-Man Broadway musical accidents, in which actors portraying Spider-Man from the critically disliked late 2000s musicals often fell from the faulty stunt ropes during a particular scene, resulting in serious injuries and medical attention. After defeating Spider-Man,he will say, "Aw, that was too easy! Maybe it would have helped if you'd turned off the dark!", referencing the musical again.

When you defeat Arthur (Ghost n' Goblin's) as Deadpool, his victory quote will say, "And THAT'S for lulling me into great side-scrolling adventures that were never possible to beat!" This is a reference to how the old NES game, "Ghost n' Goblins" is considered one of the hardest games in history, due to its high level of difficulty and the fact you must play through the game twice in order to achieve the 'good' ending.

When you defeat Dante (Devil May Cry) as Deadpool, he'll say, "Next time, maybe you should let Nero do your fightin' Skippy." This is a reference to Devil May Cry 4, where Nero was the main character for the majority of the game.

Unlike Strider Hiryu and Mega Man characters, Arthur does not have a death animation that mirrors his original death animation, in which he becomes a pile of bones. However, he will become a skeleton in his DLC costume when his powered-up armor shatters.

The Ancient Warrior DLC skin set was supposed to include a new skin for Magneto. This skin was taken from the Marvel event "House of M" where Magneto's daughter the Scarlet Witch changed the entire world. The skin generated controversy because it looked like King Juan Carlos of Spain.

Magento will reference his son, Quicksilver, when he wins a fight against Dante. "Brash, arrogant, rude, even a white head of hair... You remind me of my son in many ways."

When Wolverine is first in your party and goes up against Frank West (Dead Rising), Wolverine will say "Me and Guys named Frank don't get along so well..." this is a reference to Frank Castle, A.K.A. "The Punisher". Wolverine and The Punisher have a long running distaste toward one another.