We've driven from SE Houston (Clear Lake area) twice with the most recent being July 2009. We split the drive into 2/3 & 1/3. If we're leaving in the morning, then 2/3 of the way from Houston to Orlando is Marianna, FL and there are several hotels to choose from there. On the return trip, 2/3 of the way back home puts us in Slidell or Covington, LA (only about 20 miles apart).
Alternately, in July we left mid-afternoon and drove 1/3 way on the first day to Slidell and the 2nd day was pretty easy too! We were very fortunate and didn't hit traffic even though it was July 4th weekend!
Our drive back home was so smooth with no traffic slow-downs that we said we'd actually consider driving straight through instead of stopping, but we don't have young kids (DS's are 10 & 13).
I kept a log of drive times so let me know if you want info about specific times and I can look it up.