Spider-Man: No Way Home assembled possibly the largest group of Spider-Man characters in one movie ever. Many of his most important enemies and allies were on screen in the movie but there are several major Spider-Man characters from Marvel Comics who have yet to appear in the MCU. Some of them count among the most significant Spider-Man characters in the comics.
Major villains like Black Cat have yet to appear, along with major variants of Spider-Man like Miles Morales. They will likely emerge in the MCU at some point in the future given their prominence in the comics. But some major Spider-Man comics characters may never appear in the MCU given how different a path this version of live-action Spider-Man has charted.
Sinister Six
Despite the massive assembly of villains in Spider-Man: No Way Home the MCU has yet to properly show the Sinister Six. Comic book fans know the Sinister Six is one of if not the, greatest supervillain teams in comics and fans still want to see the actual group.
While the MCU has come very close, the core group remains one of the major Marvel Comics elements of Spider-Man lore that has curiously never made it to the screen. It will likely happen someday, but it could happen in the Sony Marvel Universe.
Uncle Ben
It seems unlikely Uncle Ben will factor in the MCU going forward, and his absence from the franchise is one of the biggest departures the MCU has taken from classic Spider-Man lore. Uncle Ben is fundamental to the backstory of Spider-Man, but he's barely been referenced in the MCU.
His role in the comics has essentially been played by Aunt May in the MCU and her more engaged role in Peter Parker's maturation and evolution as a hero has been as rewarding as Uncle Ben's. Still, fans would like to know more about the MCU Uncle Ben.
Hobgoblin
Hobgoblin is one of the best Spider-Man villains from the comics and one of the most significant yet to appear in the movies. He seems like a natural choice for a villain in the future of the MCU, but it also seems that he may not be exactly what fans expect.
In the comics, Hobgoblin was revealed to be Ned Leeds. Ned in the MCU seems to be going in a different direction, developing a talent for magic that is likely to take him on a different path than becoming a dangerous Spider-Man villain.
Robbie Robertson
Robbie Robertson is a major figure in Spider-Man's life in the world of The Daily Bugle. He's a counter to the bellicose J. Jonah Jameson and a er of Spider-Man and his absence from the MCU is notable as most of the Daily Bugle characters have appeared.
The Daily Bugle has just become a factor in the MCU, so Robbie Robertson may emerge going forward as a tonic to a much more aggressive Jameson. It could be also The Daily Bugle doesn't become the axis in Peter's life in the MCU that it is in the comics.
Cloak And Dagger
Cloak and Dagger first appeared in Peter Parker, the Spectacular Spider-Man #64 in 1982 and have been generally associated with Spider-Man ever since. They're among his most significant comics allies who have yet to appear in the MCU.
Though they've been the focus of a Freeform streaming series in the last few years, they're not part of the MCU proper yet. They will likely appear in some form shortly especially as the MCU delves deeper into magic. Cloak's powers derive from D'Spayre, one of Doctor Strange's most powerful villains.
Mephisto
Mephisto is one of the most powerful magical beings in Marvel Comics but he has a strong link to Spider-Man. He is responsible for the dissolution of Peter Parker and Mary Jane's marriage in the comics, erasing it from reality in One More Day.
The concept of erasing Peter Parker's life is now an aspect of the MCU and it's possible Mephisto could be part of the evolution of that concept. He's a character with deep connections to other characters like the Scarlet Witch and Doctor Strange and seems inevitable in the MCU.
Harry Osborn
Harry Osborn was Peter Parker's best friend in the comics for much of his early history. His absence in the MCU is notable and No Way Home implies he may never appear. Norman Osborn seemed to indicate his son is not present in the MCU reality.
Norman's ultimate fate was to become a variant of Green Goblin in the comics and it still could be in the MCU if a variant of the character somehow crosses over in the future. Otherwise, he's a major character who could end up never appearing in the franchise.
Spider-Gwen
Spider-Gwen is one of the most significant Spider-Man characters not to appear in the MCU. It's unknown if Gwen Stacy exists in the MCU but now could be the opportunity for her to appear, with Peter painfully excised from the lives of the people he loves.
Gwen Stacy could be part of the new life he builds for himself and that could lead to her becoming Spider-Gwen. She's all but certain to appear at some point, given how popular she is in the comics and now animation as well.
Miles Morales
Miles Morales has been teased in the MCU already, with a reference in Spider-Man: Homecoming. He's yet to appear though and he's one of the most important Spider-Man characters from the comics who still hasn't come to the big screen.
Comic book fans know Miles Morales became Spider-Man in the Ultimate Comics universe of Earth-1610. He's since crossed over into the main Marvel Universe and has become a major figure in Spider-Man lore in the comics and other media.
Black Cat
Black Cat is arguably the most significant Spider-Man villain who has yet to come to the screen in any form. Felicia Hardy is a major part of Spider-Man's world in the comics, walking a fine line between villain, hero, and sometimes romantic interest.
Black Cat is all but certain to appear in the MCU in the future as a villain given her iconic status and the lack of other major villains still on the board. Her connections to the Kingpin, who gave her superpowers in the comics, could also play a role.