To be honest I don’t see how they can do the Civil War story without Spiderman and the X-men. A school being blown up by an X-men villain started it and Peter Parkers coming out provided a lot of good material.
I never read Civil War. My time for entertainment is very limited and comics had to go, though I still love to discuss theoretical fights or the psychological underpinnings of the characters and other nerdy stuff.
They still do the themes that were present in Civil War and adopt them for the movie. There are other characters in the Marvel Universe that aren’t exclusive to any studio at this point that they could substitute for the important points in that series
Probably the biggest difficulty with the Civil War storyline is how do you go about unmasking and publicizing real identities of secret identities, when most of these individuals in the Marvel movie universe have been operating either unmasked or their real identities are already pretty much known already?
For example, how many times has Peter Parker shown his real face in the Spiderman movies?