Definitely worth checking in at Downtown Disney. Do it first thing and then spend the day in Disney. We checked in, discovered then and there there was a long delay on the flight and had a fantastic day in Disney rather than being stuck in the airport. If you're able to, Twilight Checkin at Gatwick is good to since you don't then need to queue the next day and it's much more relaxed. We do it but we do only live 30 mins away from Gatwick so its easy to pop in the night before!
When you land at Orlando, you have to collect your luggage at baggage reclaim and then you have to check it in again in order to use the transit to the main part of the terminal. Then you have to wait at another reclaim to collect your bags again. It's a PITA.
Cusyoms & Immigration is a nightmare - be prepared for queues. It's tedious and your children will no doubt get bored.
Is your car hire through Dollar? The car pick up is in a multistorey carpark so keep an eye on your children so they don't wander off. I think this is true of most of the car hire firms. Getting your car can be time consuming too so again, be prepared for the children to get bored.
You will undoubtably get lost at some point in your journey to your first hotel. DH & I inevitably spend at least half of the drive not talking to each other. American roadsigns are cr*p (sorry to any Americans!!) and you'll be tired and irritable after the flight (and all the queueing I mentioned)
Seating wise, I'd go for all in a line, starting from the window and ending up with 1 or 2 in the middle seats. This should mean that you're disturbed less by people needing to get out of non-aisle seats. As for where in the plane, when we've flown Virgin, seats numbered around 25 were in a small cabin of about 6 rows, just behind Upper class. Fab as it felt more private. Ask about the layout of the plane when you check in.