Sisters tries really hard. Tina Fey and Amy Poehler certainly have chemistry and some of the best moments of the movie come from that chemistry. Still, the film falls flat on its face more than once.
The movie is mostly cringe humor. It's filled with one character or another doing something embarrassing. While this can be done really well if used correctly, Sisters seems to hit everything with the cringe hammer until it cries.
This isn't really expected, and neither is the abundant use of bodily and sexual humor. There are some great moments in the movie relating to these, as well.
The real issue with the movie is it feels like the writers went at it with a list of "funny" situations and tried to fit them all into a loose theme. Throwing everything against the wall to see what sticks inevitably means there will be a bunch of junk laying on the floor.