I'd like to see them do the Justice League Unlimited animated series lineup, it worked great.
The problem is gonna be that they need a big enough threat to warrant the whole League, but if they to an alien invasion they risk looking like copycats to the Avengers.
I'd almost vote for Gorilla Grodd as the villain for this reason, but that might come across too silly for live action. You could do aliens, I think, but only if you take the fight to space, capitalize on the JLA tower and the more out-there stuff like GL. But I think the most likely is Braniac/Luthor, they work well together, have enough outlandish tech in Braniac for the visual effects, and enough charisma in Luthor to anchor the human part.