We drive from Grand Rapids when we go down for spring break. We usually leave on Friday afternoon, around 3pm, and drive until about 10pm. On Saturday, we drive all day, usually stopping around Lake City, FL. This way, on Sunday, we can sleep in and only have about a 2-hour drive in WDW and arrive rested. For the return, we leave early Friday morning, usually by 9am, and drive until 10-11pm. Saturday morning, we repeat the process and end up back home around 10pm. That leaves us Sunday to recuperate before back to school on Monday.
I definitely prefer flying, but driving is tolerable. I work nights (12-hours in an ambulance) and DH works days (12-hours in a police cruiser) so we are both accustomed to long hours in a vehicle. Our kids are 9 and 7 so they are still a little too young for me to consider driving straight through. I prefer to spread it out because I don't want to arrive and then need a day to recover.