I spent some time commuting to Jacksonville for medical reasons. I drove up Monday AM and returned Friday PM for many weeks. The easiest and most consistent time wise with very little traffic was: 301 to Bellview, 25 to Silver Springs, 40 to 315 through Ft McCoy, Interluchen, to 315C to 21to Middleburg, to 23 a toll road to 10 to Jacksonville. From my home to Shands Jacksonville was consistently under 2 hours. More small towns, mostly 2 lanes, some lights, but almost no traffic until I hit 10. No speed traps, lots of passing places more scenic and a much more pleasant drive then any other way. And I tried them all.
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Life is to short to drink cheap wine.
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