We take I-69 from northern IN thru Indianapolis, Louisville, Nashville, Birmingham AL, Montgomery, AL on I-65. Then catch US231 down to I-10 thru Dothan, AL. From there we go along the west side of FL via US19 (4-lane). You can then catch US98 over to I-75 then south.
You can go through Sarnia/Port Huron and stay on I-69 following the route above. Indianapolis is no problem with I-465. There is some construction through Louisville at the Ohio River. Working on a new bridge. Nashville traffic has never been a problem for us pulling our 5th wheel. There's often construction along nearly every route, but timing is always the trick.