The foundations that Sony is establishing for The Sinister Six movie don’t make any sense for the team to ultimately fight Spider-Man. Sony's Spider-Man Universe has had an inconsistent run so far, with the success of Venom and Venom: Let There Be Carnage offset by the relative disaster (critically and commercially) of Morbius. Yet, with audiences waiting patiently for Spider-Man to properly turn up in either Venom 3 and/or The Sinister Six movie, the web slinger's inclusion as a hero is actually impossible given how Sony's Spider-Man Universe is being built.
The Sinister Six has been teased before in The Amazing Spider-Man 2, and while that spin-off movie from Drew Goddard was canceled, the villain team-up concept was put to good use in Spider-Man: No Way Home. The Sinister Six movie is now back on the agenda for Sony, with Morbius' end credits sequence hinting at what's to come. Michael Keaton’s Vulture arrives from a parallel universe (complete with his Vulture flight suit), suggesting a team-up with Morbius in order to “do some good.” Though it's unclear which Spider-Man (Tom Holland, Andrew Garfield, or even Tony Maguire) would be in The Sinister Six movie, it seems inevitable that Spider-Man will show up for the villains to fight.
The problem that the Sinister Six movie has, however, is that the reason for the members to team up (to “do some good”) is completely at odds with their comic book heritage, where the villains joined forces to kill Spider-Man. With Sony lining up Spider-Man’s villains to all be anti-heroes, the studio is giving itself an impossible task and heading for disaster by making a rod for its own back. Though in the comics The Sinister Six team up for their own selfish and personal reasons, they are under no illusions that they are the bad guys, and revel in their villainy. Inserting Spider-Man into The Sinister Six movie where the villains are trying to do some good is the opposite of their usual reason for existing, and isn't nearly as interesting on paper. Inevitably conflict with Spider-Man would have to be shoehorned in, and it would be far better for the villains to embrace their true nature in the first place.
Audiences have responded well to Venom being a lethal protector and a force for good. However, that will have to change if he’s going to satisfactorily fight Spider-Man without it seeming underwhelming or the audience rooting for Spider-Man to lose in order for Venom (or any other members of The Sinister Six) to win. Captain America: Civil War has shown that there is scope to have two sides believing they’re in the right, but in that instance, they were all heroes in the first place. To create a great Sinister Six movie that honor's its roots, the villains need to be bad from the off to present a threat worthy of Spider-Man and give Peter Parker’s task of defeating them feel right. Changing motivations halfway through or altering character traits sets up The Sinister Six for disaster.
Conversely, Vulture's notion of doing good could potentially be interpreted as killing Spider-Man. However, Morbius' response to the idea as being intriguing doesn’t quite fit, as there is no indication that Morbius sees his universe’s version of Spider-Man as a threat. Whether Kraven The Hunter can steer the villains away from disaster remains to be seen, however having The Sinister Six be the heroes of their own movie makes it impossible for Spider-Man to be a part of it.
