We will sometimes gamble and start out with a whole row, booking windows and aisles of a row, and leave the middle seats empty in hopes that no one selects them. For less busy times/flights, this has worked. A couple of times, we have offered to trade with one of the middle seat passengers, which they gladly and graciously accepted, which then put us all together, with one parent across the aisle. This seems to work well as a strategy for the elite seats, where you have to pay extra for more room, because who wants to pay extra for a middle seat? They seem to be the last to get selected. We get access to the "more room" seats at no extra cost on AA with my husband's status, so it works out.

However, when we still had a toddler, we went 2x2, with one parent wrangling each kid. Kid in the window, parent in the middle. Sometimes, we'd employ the same approach with consecutive rows on one side. Depends on what's available.

Our boys are 5 and 7 now, and they get completely absorbed in the IFE and require very little minding, so having my husband across the aisle almost next to me is actually a nice treat after ~4 years of him being one row up.