We drove to visit my family in the DC area from Indianapolis over Christmas. We hadn't made the trip in a few years. The kids were 3.5 and 20 months.
They were such troopers. We chose to go straight through for the very reason you indicated - we didn't want to deal with having to pack and unpack the car on multiple occasions.
We always make sure the car is packed with snacks, milk, backpacks with toys. We had a DVD player that was the saving grace.
My other advice is to make sure to take scheduled stops ~ every 2-3 hours while they're awake to help release pent-up energy. In our experience, they don't really sleep well when in their car seats for long periods of time (especially if they're prone to being active sleepers anyhow). We have tried the late night, through the night thing, only to have one kid wake-up when stopping for gas, not going back to sleep and being thrown off their schedule entirely.
We found places like Walmart and Target were Godsends for us - lets the kids stretch their legs, load back up on drinks, etc. if needed, and back on the road for a few more hours.
Good luck!