Welcome aboard the RoadTrip America Forums!

For the most part, the drive from Wisconsin/Chicago(?) to Gainesville can be done on the flat, and the Interstates you mention (I-65 to Nashville, I-24 to Chattanooga, I-75 to Gainesville) form the most direct all-Interstate route. You'd see some minor grades around Chattanooga as you skirt the very southern end of the Appalachians but nothing to be too concerned about.

However, something that I'd worry about even more than hills (Interstate slopes are limited to 6% grade, maximum.) is traffic, particularly multi-lane freeways with frequent exits and entrances, large speed differentials between vehicles, and frequent lane changing. In other words, large cities, e.g. Chicago and Atlanta. There are ways around those cities that I would strongly suggest that you at least consider.

If you are truly starting out from Wisconsin rather than Chicago, I-43/I-39 south to Bloomington and then I-74 east to I-57 south lets you swing well around Chicago and also miss Indianapolis. You'd then get on I-24 in southern Illinois rather than in Tennessee. To avoid Atlanta, you'd stay on I-65 south out of Nashville all the way to Montgomery AL. From there use US-231 south to I-10. While not an Interstate highway, US-231 is near-freeway quality for almost the entire length you'd be driving it. I-10 east would get you back to I-75 south to complete the journey to Gainesville.

While it's true that those two alternatives would add a bit of time and distance to your drive (roughly 70 miles and an hour and 15 minutes), that's fairly minimal on a trip of this length. And the advantage of missing at least two large driving nightmares (Chicago and Atlanta) make them well worth it in my opinion.

AZBuck