For us it would depend on the length of the flight. For a short flight (say up to 2 hours) I would aim for the 3+1 option. But for a longer flight I would aim for 2+2 option. The main reason that a longer flight is likely to include a meal service of some type (even if its buy-on-board or byo) and one parent supervising two young feeders may not be overly successful.

The younger the children the more I would tend towards the 2+2 to provide one-on-one supervision/entertainment. If the kids are a little older and interact well, then 3+1 can allow the kids to entertain each other.