MCU: 10 Best New Villains Who Could Join Phase 4
4. The X-Men/Fantastic Four
This is obviously a slightly more left-field interpretation than the introduction of just a "normal" villain, but it would be a great way to introduce either the X-Men or the Fantastic Four and not have to change the established foundation of the MCU too much.
An inter-dimensional rift could work to bring an established X-Men or Fantastic Four team to the MCU's Earth, with the government wrongly interpreting them as a new alien threat and despatching their heroes to deal with the issue. That was we could have the popular X-Men v Avengers story arc without having to turn anyone legitimately evil, and it would be a novel approach to the usual origin story model.
The sudden arrival of mutants would be best suited to this - particularly as it stops the need to retro-actively explain their being MIA currently - and seeing familiar characters throw down would be a huge ticket seller.