[SteveZ]

Have tried several different routes. I-10 to US 301 to Rt 24 (at Waldo) to Gainesville to Rt 331 to I-75 to Rt 484 (Exit 342, I believe) to Rt 475 to Rt 466 works for me. It's the shortest and has the least headaches for construction and delays.

Every other way adds considerable mileage and time. I-95 south of JAX can be a royal construction mess, and if there are any fires, the smoke across the road is miserable.