We used to drive it every summer (fromRI) when our kids were little. My DH loves the drive - I hate it. We'd do a lot of night driving while the kids slept, and usually stop halfway down. The advantages are that you can bring more with you, it's considerably cheaper, you have use of your own car. The disadvantage, besides the long drive is that it's much safer, statistically, to fly. We were lucky in that our kids are great travelers, but if your kids need constant entertainment, it can be really difficult.
You do realize that by using statistics you find that it is also safer to walk a tight-rope than to fly... The trouble with statistics is that they are easily manipulated... That said, there is a couple of question only the OP can answer, what time of year will you be driving and on what days would you be heading out... I ask that because I personally don't enjoy driving in the dark and if its a winter trip you don't have a lot of daylight... If its a summer trip then it isn't a problem... But when you are heading out can be a big concern since he lives on the east coast. I know when I lived in Connecticut I was very careful when planning long trips through the NY/NJ area because the traffic during certain times is maddening.
The other question is can you afford to lose 4 days on the road... Not sure how long the total vacation is but if you are going to give up 2 days down you will also be giving up 2 days back... will that hurt your total vacation?