Throw in Mysterio (assuming he is indeed nefarious) and some other Spidey villains we haven’t seen in the MCU yet, like Kraven the Hunter, Chameleon, Doctor Octopus, etc, and you have yourself a solid lineup of antagonists working together.
This could be how we finally see Mac Gargan could become Scorpion, and perhaps something would push Vulture to wanting to target Peter again.
It’s possible, though, that even if Sinister Six were to still be made, that wouldn’t necessarily prevent the MCU from putting together its own version of that team, even if the members don’t necessarily call themselves that.