We've made the drive from the Philadelphia area 8 times now. I know that's the opposite corner of the state from you, but I'll share our experience. When doing the drive over 2 days, we usually stop in Port Wentworth/Savannah (on I-95) the first night. That gives us about a 4 hour drive the next morning. We used to make reservations at the Comfort Suites there (we usually have 3 or 5 kids with us so we need a suite) but there are many options.
Honestly the last several trips we haven't made reservations anywhere and we haven't really had any trouble finding decent hotels (usually staying at a Choice Hotels or Hilton property. We have never stayed at a crappy roadside motel -- I'm much too high maintenance for that. lol.). When we're ready to stop for the night (usually around 6:00 p.m.), we just get off at an exit with several hotels. We'll park somewhere and use Expedia, Hotels.com, or similar website to find and book a room. There have been a few rare occasions (maybe twice in 20+ hotel nights) when we've had to drive to the next exit to find a hotel with vacancy, but it's never been a big problem. This plan might not work as well if we chose to drive until 8 or 9:00 at night as more rooms would be occupied by then. The one time we did want to drive a little later, we still pulled over at 6:00 and booked a room based on where we planned to drive to that night. It's a lot easier to estimate where you'll be in 2 hours rather than where you're going to be in 2 weeks before you've even left your driveway.

If you do decide to book a room before you leave, I strongly suggest booking something that can be canceled by 6:00 p.m. with no penalty as you just never know how the weather and traffic will affect your drive. On one trip (that we thankfully hadn't made advanced reservations on) there was a huge accident on I-95 in VA. The road was closed in both directions for most of the day and traffic on the alternate routes was horrendous. We had planned to drive to the southern end of NC that day but only made it to southern VA. Fortunately we were doing the drive over 3 days that trip so it really wasn't a big deal, but we wouldn't have wanted to keep driving to the town we had planned to stop in just because we had made a hotel reservation there.
We just got home from a road trip to Texas and used this same strategy for hotels for that drive. Worked great.