An obvious choice if wanting to avoid super slabs is US-60. However, US-60 does a lot of meandering between Paducah and Louisville. Also, I wouldn't recommend US-60 through either Louisville or Lexington. The Western Kentucky Parkway is a limited access divided highway but not interstate. You will still have high speed riding and semi-trucks but in a more rural setting. The parkway is my preferred route.
US-60 to Paducah
I-25 to the Western Kentucky Parkway (about 25 miles)
Western Kentucky Parkway to I-65 at Elizabethtown (about 150 miles)
I-65 north to the Bluegrass Parkway (2 miles)
Bluegrass Parkway to US-127 (about 60 miles)
US-127 north to I-64 at Frankfort (15 miles)
I-64 east to Winchester (about 43 miles)
This route avoids Louisville completely and takes you the fastest route (I-64/I-75) through Lexington. The interstates in Lexington will be congested but the alternative of driving through town would be stop and go and congested. There are rally no good routes from the the south. Another alternative would be to stay on US-127 and not take I-64 but go all the way to US-460. US-460 will take you through Georgetown and Paris. At Paris head south on KY-627 to Winchester. That alternative route would add several miles to the trip as you will be quite a bit north of Winchester when you are in Paris. (FYI - the trip on US-460 between Frankfort and Paris is a gorgeous trip through horse country.)
