a sequel isn't just "feasible", it's guaranteed. I know Ruffalo is signed for 6 films, some of them Avengers movies. I imagine the rest of the cast is in the same boat.
Shit happens, so its possible an actor or director might have to be replaced. oddly enough, since SHIELD and its links to the characters has already been established, there's no reason to shoehorn them in again. We already know they will work with SHIELD if asked.
That being said, completely expect that any individual movies coming out after this WILL have some kind of tie to Avengers 2. it might not be shield, and it might not be a superweapon, but there will be something. As for "a nightmare for writers", writers familiar with comics have been dealing with 40 or 50 years worth of backstory when putting arcs together. One movie is nothing.