Reed and Ben do not know each other from before the flight, and they are not best friends. This makes Ben's reaction towards becoming the Thing much more aggressive.
Reed and Victor Von Doom's rivalry is gone, as the two never met before the events of issue 2.
While Ben Urich was friendly with both Peter and Spider-Man in the main universe, in Spider-Man Noir, Ben helped Peter get a job at the Daily Bugle and became a close friend and mentor to him. Ben was also present when Norman Osborn had Ben Parker killed and tried to atone for this by helping Peter (since he had been taking bribes from Norman). While Ben's jaded cynicism clashed with Peter's youthful optimism, the two were close to the point he unintentionally encouraged Peter to keep fighting for justice, and his death was more motivation for Peter to be a hero. In a way, their relationship is not that different from the one between Peter and Tony Stark in the Marvel Cinematic Universe about seven years after the first comic.
Peter's friendship with Robbie Robertson, who is roughly Peter's age and a fellow reporter, is much closer than in canon. He is close friends with Peter and has never met Jameson, giving them a far different relationship.
The premise is about Mary Jane and her childhood friends Liz, Flash and Harry as they attend Midtown and deal with the frequent problems they face, while Mary Jane herself deals with her crush with Spider-Man while developing a closer friendship with Peter Parker. This is all wildly different from the original comics.
Dialogue seems to indicate that Mary Jane has a strenuous relationship with her mother instead of her father.
Flashbacks reveal that Mary Jane dated Ned Leeds in the past.
Spider-Man: Life Story: In 616 and other AU, Aunt May and Mary Jane always had a very close relationship, with both of them seeing each other as surrogate daughter and mother. In this series, MJ comes to have issues dealing with May's dementia, especially when the latter nearly endangers and loses MJ's babies on a stroll in a park.
The Mighty Thor: Loki is portrayed as the title character's brother, having been adopted by his father, Odin. In Norse Mythology, Odin and Loki were more along the lines of blood brothers. note In the first comic depicting Loki's backstory, it was accompanied with a note saying, "Many are the legends of Loki's birth--but this is one we favor!"
In the comics, Elektra and Bullseye were rivals competing for the Kingpin's favoritism and the two mutually despise each other. Since she's not a villain, this is absent in the film. She doesn't even see Bullseye, much less meet him, until the two fight and her hatred towards him is more personal.
In comics, Elektra was Bullseye rival and the two shared a mutual dislike of one another. Since Elektra doesn't work for the Kingpin, she's just another target for him, albeit one he finds very attractive.
Spider-Man: Into the Spider-Verse: In the Spider-Gwen comic, Peter Parker had a secret crush on Gwen Stacy, who was his classmate and long-time friend, and became jealous when she went out with Harry Osborn. Due to the age difference, it can be assumed their relationship was different here. Subverted in Spider-Man: Across the Spider-Verse, which reveals they were the same age and childhood friends like in the comic. It's also implied Gwen and Peter had mutual feelings for each other, as they were apparently going to prom together before he became the Lizard.
In the comicsnote until she finds out Peter is Spider-Man, pre-Brand New Day and most adaptations, May Parker's afraid of Spider-Man and, like Jameson, thinks he's a menace. Here, at least when he saved her from Doc Ock, does she see Spider-Man as a real hero. The opposite goes with her views of Doc Ock, whom she thinks is a nice man (and almost married him) in the comics.
In the comics, Peter Parker dated Betty Brant for a while, before pursuing other romantic interests. Even though there is a slight hint of sexual tension between them in the films, they never get together.
X-Men Film Series: In the comics, Phillipa Sontag/Arclight was a member of Mister Sinister's Marauders, who once caused a massacre of Morlocks. In the film, she's in the same team as the leader of the Morlocks of all people, Callisto.
Downplayed as this only happens after some Character Development, but this might be the only adaptation where Bruce Banner sincerely thanks Hulk and vows to see him as more than with the distain he had for him for years, even calling him a gift. Hulk, in turn, seems to be more cooperative with Banner's wishes.
In the comics, George Tarleton and Monica Rappaccini dated for a while. Here, the relationship is completely professional, and when he discovers how long he was a lab rat at her hands, he attempts to kill her.
In the comics Bruce Banner and Monica Rappaccini get along really well even though she's a villain. They've even teamed up more than once. In the game, their relationship is purely antagonistic, though she is his ex-girlfriend.
Downplayed in the case of Kamala's relationship with her father. They have a good relationship in the comics, but she's generally closer to her mother and doesn't confide in Yusuf as much. In the game, it's the other way around.
Peter Parker and Miles Morales usually either don't exist at the same time (or in the same universe), or at the very least don't know each other. Here, Peter becomes his Big Brother Mentor before Miles gets powers of his own and by the time of the DLC, his Parental Substitute and mentor, in effect Miles' Uncle Ben, taking over after his father Jefferson died.
In his origin in the comics, Otto Octavius had no prior relationship to Peter Parker before the accident that led to him becoming Doc Ock. Here, his relationship to Peter is much like Dr. Curt Connors and George Stacy, being his Scientific Mentor and Parental Substitute respectively. This is likely a Shout-Out to Spider-Man The Animated Series, where Octavius had a somewhat similar relationship with Peter when they were younger (there, he was a mentor to Peter at science camp when he was a kid), and to a somewhat lesser extent, Film Spider-Man 2, where they have a non-professional relationship when they're both adults, but still meaningful.
Strangely, this happened to both sides of the same character he gets this treatment with himself. In the comics, Mr. Negative was something of a Dr. Jekyll and Mr. Hyde; both Martin Li and Mr. Negative were separate entities and aware that the other existed, but not of what they did. This version of Martin Li and Mr. Negative are one and the same. While there are hints of Negative being Li's Superpowered Evil Side, Li doesn't have a split personality and thus is consciously Mr. Negative.
In the comics, Norman Osborn's sociopathic behavior pushed his wife to fake her death to get away from him and he sold Harry's soul to Mephisto to ensure that Oscorp would be successful. Here, Norman truly loves his family, Emily Osborn really did die of a genetic disease that Harry inherited, and while Norman certainly doesn't mind the wealth and power the corporation has brought him his primary motivation is to use Oscorp's resources to find a cure for Harry's condition.
Among the many changes to the Tinkerer in Spider-Man: Miles Morales is that the character is Rick Mason's youngersister, not Rick's elderly father as in the comics.
In the comics, Alistaire Smythe builds Spider-Slayers because he blames Spidey for the death of his father. In this cartoon, he sides with Osborn against the Jackal in the Enemy Civil War to get out from his father's shadow, and enthusiastically pits his Slayer against Spencer Smythe's.
This version of Black Cat (Felicia Hardy) isn't romantically interested in Spider-Man, unlike other incarnations.
Spider-Man (1967): Peter Parker and Betty Brant were dating in the comics when they met as teenagers, and Betty was wary of Spider-Man. This version of Peter and Betty have a more platonic relationship with each other, and Betty is more supportive of Spider-Man.
In the comics, Felicia Hardy and Peter Parker met as Spider-Man and the Black Cat originally and had no connection to each other prior to that. In this series, she and Peter are classmates before she becomes the Black Cat. She also wants to know Spider-Man's true identity despite the comics version of the Black Cat initially not being interested in who Spider-Man was behind the mask. Also, she and Peter never learn each other's true identities in this continuity unlike in the comics.
In the comics, Hydro-Man and Mary Jane Watson have never even met, and they have no connection to each other in the slightest. In this series, Hydro-Man is reimagined as Mary Jane's crazy ex-boyfriend turned super-powered Stalker with a Crush.
The Spectacular Spider-Man: Sandman (Flint Marko) and The Rhino (Alex O'Hirn) act as a duo before gaining superpowers. The two never met before in the comics until after gaining their powers.
In both the original and Ultimate comics, Aunt May doesn't trust Spider-Man. Here, she doesn't seem to acknowledge him in anyway. Presumably because she's been aware he and Peter Parker are one and the same.
In the original comics, May has a crush on Doc Ock. Here, she sees him as the dangerous criminal he really is.
Wade Wilson/Deadpool and Taskmaster underwent this In the comics, they're BFFs, (Vitriolic Best Buds, but still rather close allies). In this, they're a lot less friendly towards each other as the fact that Wade has no prob "unaliving" him freaks Tasky out.
