we've driven 5 times in the past 3 years from NY w/ 2 small kids...
some of my tips.... always have ressies for where you'll stop, especially if you have kids with you. we didn't once, and while you'll usually be fine w/out ressies, this one time there was some sort of convention near I-95 and every motel was fully booked for 60 miles! no kidding!! we had cranky kids in the car, it was 10pm, dark, we didn't know the 'safe' exits from the unsafe ones, and it was getting scary (and there are a lot of unsafe exits on I-95) and we were exhausted and needed to sleep! it's also nice to have a destination, instead of saying to each other 'should we drive another hour??'... we have an 18 hour drive, leave home around 5am, drive the equivelant of 10 hours (usually takes 12 hours including nice reststop breaks), get to our motel, dinner and bed. then leave around 7am and get to disney around 4pm.
oh, and i've found the local Chamber of Commerce for whatever area i was thinking of staying in overnight very helpful. i called (as opposed to looking on-line) to speak to someone, and i've had the nice people tell me which exits were 'safe' or unsafe, which were newer w/ better restaurant choices, etc. They are always very helpful.
we do the wrapped gifts too for the drive. when i told my kids we were going to disney again (we're leaving in 3 weeks!), the first thing they both said was "yea! we get car presents!!!" I do dollar store stuff, regular toys and craft activities. that and the dvd player make our trips wonderful! we actually love the drive!
dh insists of bringing all the luggage inside the motel on the way down. he says those motels are "marks" for burglars and won't take a chance of getting broken in. imagine having your window smashed on vacation and not being able to get on the road the next day.
I have the "Drive I-95" book - look on-line to order it. I love it and just got the new edition for a friend who is going to florida soon. We've marked down the good and bad exits (easy on/easy offs, dangerous looking ones, safe looking ones, etc) the past few years.
We bring food for the first day and stop in the very nice state welcome center reststops (the ones that have no restaurants, but lots of picnic areas, etc). The kids run around the grass, we bring jump ropes and have a nice break. Dinner is a restaurant near the motel. The next day we do the free motel breakfast, mcdonalds or something for lunch, then we're in disney for dinner. Doing the picnicing the first day and restauranting the 2nd day works well. we don't have to worry about a cooler or ice, but have nice picnic food the first day and the kids being able to run around is much better than them having to sit down in any kind of restaurant. I like the mcdonalds playarea idea (i think i even read somewhere you can look on-line at a mcdonalds site to map all the playarea ones), but we're sort of germ-o-phobic, especially on vacation, so we do the rest stops instead.
I bring some snacks for the car, but it's so much fun for the kids to pick snacks when we get gas, etc, that i let that be the majority and just bring enough for emergency hungries. same goes for snacking while at WDW - we really don't bring anything except a couple of granola bars for emergencies. the kids (and me!) want WDW snackies!!
we always bring our potty in the back of our suv (we even brought it when we took our car once in the trunk). with kids there are too many times they need to go and we can't find a clean restroom (or safe area). we LOVE our potty for the kids (and they're 6yo and 4yo and don't "need" it, but we've used it tons!) And we always line the potty w/ kitchen garbage bags to pull out and throw away with each use, instead of having to empty and clean a potty. yuk!
that's all i can think of for now. i love reading others tips! thanks to all!