IF it's an accurate reflection of the cast, I think we can already start to see the contours of the plot...
A multiversal incursion (likely investigated by Doctor Strange) results in the Fantastic Four and their Doctor Doom entering the main MCU, and Sam Wilson Cap has to scramble to put together a ragtag Avengers team mostly comprised of whoever survives THUNDERBOLTS, the FF, and Strange (and a reformed Wanda?) to thwart Doom.
It's risky, though. Leaning very heavily on RDJ to generate the big star/character power.
No Spider-Man and Star-Lord is the biggest surprise (because Spidey is the most popular Marvel character and Chris Pratt is one of the more popular MCU actors to the average audience).