No superhero is complete without the rotating cast of villains, anti-heroes, and antagonists that make up their rogues gallery. An ensemble cast of opposing forces, each with their own personality and motivation, is one of the most intriguing aspects of comic book lore.
Sony has shown no signs of slowing down in their grand scheme to adapt Spider-Man villains to the big screen in ambitious solo projects with mixed results. Venom was a mixed bag, Morbius tried but failed, Kraven is next on the chopping block, and no one seems to know who El Muerto is, but surely Marvel's most beloved hero has some better bad guys.
Doctor Octopus
One of the biggest problems of the Sony Spider-Man Universe films is the misguided way they attempt to turn villains into heroes. Sure, both Venom and Morbius had moments of anti-heroism in their comic book runs, but they're antagonists first. Doctor Octopus could work on a very different level. Doctor Otto Octavius is a difficult and tragic figure with a self-contained history and solid mythos.
There are a ton of great stories about men driven mad by their own hubris, transforming themselves into a monster as they turn against the world. Despite his obviously silly name, Doctor Octopus has an origin story that stands easily on its own, without Spider-Man. The tale of a gifted scientist turning to a life of crime after accidentally killing the woman he loved and turning himself into a monster could be an excellent film. Take inspiration from the classic Universal Monsters, and make it a PG-13 horror film. Doc Ock could carry a solo movie, but it's unlikely the studio would have the guts to make it.
Chameleon
Dimitri Smerdyakov is heading for a supporting character role in Sony's upcoming Kraven the Hunter film because the identity-shifting supervillain is the hunter's half-brother. Chameleon is not cut out for an anti-hero project, but these films don't have to be about the good guy. Chameleon is a global spy and criminal, capable of taking on the identity of just about any humanoid being.
The Marvel Cinematic Universe has made a few solid spy movies, between Captain America: The Winter Soldier and Black Widow, maybe the SSU could succeed with that formula. Dimitri is an unethical monster who can place himself in any environment and infiltrate any situation. A superpowered heist film could be an excellent use of the world built across the previous SSU films.
Black Cat
Since it looks like Silver & Black won't be making it out of the pre-production phase, Felicia Hardy is still yet to make her big-screen debut. This is shocking, given that she's one of the most interesting and dynamic characters in the Spider-Man canon. Black Cat is a skilled cat burglar who inherited her mantle from her legendary thief father after a traumatic assault by a college boyfriend. Black Cat has always wavered between good and evil, she's fundamentally morally neutral and self-centered.
Without her relationship with Spider-Man, there are still plenty of interesting aspects of her story. Later writers granted Hardy some supernatural abilities, specifically the ability to affect probability fields and cause enemies bad luck. After Deadpool 2's flawless adaptation of Domino, Black Cat could feature some comparable excellent action scenes, but in reverse. Instead of situations converging in a Final Destination-esque sequence to benefit Domino, they'll conspire against Black Cat's enemies. It's a can't miss formula with a ton of interesting directions.
Screwball
A more recent and lesser-known Spider-Man villain, this internet-obsessed Parkour artist could make an interesting and unique supervillain film. There simply isn't much about Screwball out there, most probably know her from her challenges in Insomniac's Spider-Man. With that freedom, filmmakers could make anything out of her story.
Screwball is a villain with a huge social media presence who commits crimes and pulls pranks to increase her status while live-streaming. A later story depicts her taking over a film production. As a character about making media, Screwball is perfect for a meta-comedy film about making movies or social media. Though she hasn't been an anti-hero in the past, she could easily turn into a comedic hero, foiling low-stakes crimes and posting them online.
Kaine
There may be no era of the Spider-Man comic book continuity that has received more hate than the dreaded Clone Saga. The period marked by Jackal's quest to clone Peter Parker has been roundly despised by most, but Kaine is an interesting aspect of that era. Kaine is a failed clone, cursed with swift degeneration, who takes it upon himself to replace Spidey with mixed results. He slaughters his way through the criminals he encounters, but he finds his stride eventually.
The reason Kaine would make a good addition to the SSU is that he later becomes the Scarlett Spider, a comparable but different character to Spidey himself. Scarlett Spider could provide the SSU with a different direction and a ton of interesting new dimensions.