From an interview with Nick:
“And the other thing that’s really hard with comedy sequels is people want some of the same stuff, but they don’t want the same movie again,” he said. Neighbors 2 stays true to the theme of the original Neighbors, which is about the fear of life’s next stage. In Neighbors, Mac and Kelly feared becoming responsible adults, while frat leader Teddy (Zac Efron) feared graduation. In Neighbors 2, Mac and Kelly are about to have a second child and worry they’re not good parents, while the sorority freshmen (lead by Chloë Grace Moretz’s Shelby) fret that they won’t fit in at college. Meanwhile, Teddy is having a “quarter-life crisis” as he watches all of his friends better adjust to the real world.
Stoller pointed to the fact that early versions of the Neighbors 2 script once again had Mac and Kelly yearning to stay youthful and party it up with their raucous neighbors. “It would be like in Toy Story 2, if Buzz and Woody were fighting again. It’s like, 'No, they already fought, they figured their stuff out. They don’t need to fight anymore.’ So it’s figuring out the evolution of everyone’s relationships.”