Years in the future, after the deaths of Franklin and Valeria Richards, The Fantastic Four are no longer Marvel's First Family, in fact they aren't much of a family any more.
Sue Richards is under the earth seeking a ancient Kree artifact at the Earth's core, and has run afoul the Mole Man and his minions. Reed Richards is trapped in the Negative Zone, and the Shi'ar's Imperial Guard confronts Ronan While the Avengers and friends (Spider-Man, Daredevil, and Luke Cage) Join the fray. The Human Torch and The Thing enter the Neg Zone to find their friend. Sue returns to the Earth's Surface to seek the help of Dr. Strange and his daughter.
Ben and Johnny hook up with Reed as he battles Annihilus, and return to Earth as the Avengers throw down on Ronan and the Guard. Soon they are joined by The Silver Surfer, and The Inhumans. Sue returns demanding the help of her former teammates, while Nick Fury, Iron Man, Thor, the Vision, and a female Captain Marvel) who are on the SHIELD orbital space platform near the orbit of Pluto witness the arrival of the entire Kree and Shi'ar armada
Not entirely sure what is going here, but it seems to be a typical fanboy storyline that involves virtually every Marvel character in a cosmic event.
This story is so convoluted you need a scorecard.
Spider-Man makes his typical gratuitous appears because, well he's Spider-Man, and everyone else is here.