The big advantage of the Marvel Universe has always been that while it's interdependent, it's also highly compartmentalized. The world and the characters were created pretty haphazardly, and the sense of a vast, ongoing mythos or continuity was largely the invention of later writers and artists. The MCU is no different; if any of the movies or interpretations of the characters had flopped, Marvel could have ditched that component of the franchise in favor of something else.

The stable is growing, with more characters set to come online over the next phase of Marvel's cinematic and TV development: Ant-Man, Dr. Strange, The Defenders, Daredevil, Heroes For Hire, etc. But there are still huge properties that remain in the hands of the other studios, and likely will for some time. That said, not all of them might be necessary for the integrity of the larger, "canonical" Marvel franchise. Here's my rundown of the pros and cons of the situation:

  • X-Men (Fox). At this point I'm not really crazy about the X-Franchise, which seems increasingly long in the tooth โ€” it's the longest-running superhero franchise of the current era, stretching all the way back to when Bill Clinton was President. Assuming that the series ends with Age of Apocalypse in 2016, it'll probably be in need of a reboot by that point. But the X-Men were never really a core part of the "classic" Marvel brand โ€” up until the '80s, they were an oddball "outlaw" team that existed mainly on the margins of the universe. So it doesn't really hurt to not have them meeting the Avengers or traveling to Asgard. At any rate the continuities are so convoluted that the franchises are completely incompatible with the MCU.
  • Spider-Man (Sony). This is a big deal to many, since Spider-Man has always been Marvel's signature hero and the embodiment of its "superheroes as regular, neurotic folks" philosophy. And there were rumors, mostly unconfirmed, that there would be hints that the Andrew Garfield reboot would exist within, or at least adjacent to, the established MCU. But then again, Spidey, like the X-Men, tended to exist in his own corner of the Marvel Universe, with the other heroes treating him as an over-enthusiastic amateur who tended to get in over his head. It would be weirdly fitting if SHIELD did acknowledge him, but considered him too immature or weird to bother with.
  • Fantastic Four (Fox). This is the one property that I think the MCU really does need. Reed Richards is one of the great minds of the Marvel world, and not having him or the team around leaves open huge gaps in the mythos. No cosmic vistas or super theoretical science (as opposed to the applied, consumer friendly Stark model). Also, you lose many of the great villains of the Marvel Universe โ€” Victor Von Doom, Galactus, Annihilus, Immortus/Kang.