And Spidey? Well, I'm fine with him being at Sony (I actually like the Garfield/Webb take on the character even though TASM2 was a narrative mess), and pretty much the only reason I'd want to see him in the MCU would be to see him interact and Cap and Stark. Or to see him done as an expensive Netflix series. But outside of those 2 possibilities I haven't had this burning desire to see him join this universe.

t:
I voted Spidey just because I enjoy seeing him geek out over other superheroes and the likes of Tony Stark. It's like having Coulson be a Cap fan in Avengers; the geeky audience surrogate is an easy character to like. Besides, it's just hilarious if Spider-Man is out there keeping the city safe from all these immediate threats only to be constantly called into suspicion, while in the mean time the Avengers are sitting up in their private tower, sipping ice tea and waving at their adoring public.
There is a strange charm to Peter as the regular kid with terrible luck despite the fact that he's been gifted with these amazing abilities (on top of naturally being pretty damn smart). It's as if Peter's so use to be being beaten down he manages to turn everything into a burden, even freaking superpowers. Yet Spider-Man gives off the impression of someone having a wild amount of fun. I like the characterization of a younger Peter Parker as a reserved, socially awkward teenager in daily life who takes on this snarky show-off personality as Spider-Man. If Peter is your typical insecure teenager type who has grown up surrounded by these costumed heroes with larger than life personalities it feels almost natural for him to climb into a spandex suit and feel liberated by this. Plus, having older superheroes to idealize and who make the job look so awesome supply a fun contrast to Peter's own less conventional, occasionally sloppy, way of doing things.
At the same time, it's totally not a
requirement or anything. You can totally create the same basic effect by emphasizing "the audacity of anonymity" and how putting on that mask removes him from all real life expectations of how he is suppose to act in accordance to his place in the High School Hierarchy. It all still works even if Spider-Man is regulated to his own universe, and so I wouldn't say that he
needs to be in the MCU. Sure, it's possible to come up with stories where including them is a natural fit, but you could argue that while plenty of characters maybe served by being part of a large universe the majority could have their stories told entirely separately while still maintaining their characterization and themes.
I even agree with others that both the X-Men and the MCU benefit from being separate universes. They never cleanly meshed together for me, anyway. Heck, for the longest time when I was little I didn't even know they shared a universe. I read mostly X-Men, and assumed that when Spider-Man or Hulk popped up it was just a crossover gimmick and treated it like a Wonder Woman fighting Storm moment. Kind of like Sabrina and Archie; they would occasionally cross over and feature one another, but 95% of the time Archie's comics didn't deal with the supernatural and Sabrina seemed entirely removed from Riverdale. I just thought that was how comics worked.
(Actually, that eventually lead to me and my brother having a huge fight on the subject which to this day he'll bring up whenever we talk about comic related things. Maybe that's why I like them being separate now. So I can retroactively enjoy a small victory!

)
F4 is in a similar position. I think they have strong enough stories that you could keep them isolated from the other properties and still tell good stories. Do I enjoy Johnny and Spidey's friendship and would I love watching Reed and Stark having a scientific pissing contest? Yeah, I totally would. But none of that needs to happen.
In fact, I feel like limitation often breeds creativity and can really force writers to tell a better story instead of just lazily relying on other people's work. Just to use an example I'm sure will upset most people, the MCU has decided to run with Stark being Ultron's creator which, had Hank Pym been fully introduced isn't likely to happen. However, as someone who has yelled at Hank to stop wasting his time creating killer robots and go back to studying bugs, and as a big fan of watching Tony Stark suffer, I really think this is going to turn out to be a brilliant bit of storytelling.