We hauled our 5th wheel from Michigan to Florida via I-65 (from Indianapolis to Montgomery, AL where we caught US231) and back. The section from Indy to Louisville has some rough spots and I thought the area around Birmingham, AL was a bit bumpy too. Overall I'd say I-65 is about the same as most Interstate highways in the U.S......some parts good, some parts not so good.
Still, we're heading that same route this winter because I-75, which we've traveled many times, definitely has greater elevation changes and is busier than I-65. I-65 has a lot of truck traffic from Indy to Louisville, but I thought the rest of the route wasn't bad at all.