From Nashville and/or middle TN area I always opted to route myself up Pennyrile and the old US41 when going to Chicagoland or points Wisconsin. Or going back south from those midwest points.
Been taking that route for almost 20 years. I remember last year I booked a trip from Alabama to Chicago with a huge winter storm inbound. I rode slowly over snow packed roads all the way to Chicago nonstop. I-65 in Kentucky was a frozen roller rink and shut down that night for about 12 or more hours. 41 that time kept my schedule uninterrupted.
It normally only adds about a half hour to the trip (semi truck), cuts about 40 miles off of it, and the traffic is minimal regardless if day or night. The red lights in Terre Haute are not so bad during the day either. At night many times you can just breeze on through.
In recent years a lot of paving and roadwork has really smoothed it out too. It used to be really rough on some stretches. It's a nice change of pace much less taxing (no pun intended) in many ways than the I-65 route.