OP would help by letting us know what type of RV. We use 40, 26, & 95 regularly between IN and the East coast of FL to avoid 75 through GA (and of course Atlanta.) We're towing a fifth wheel with a diesel pickup. "Safest" is tough to describe, but I think our route is safer than 75. You must be ready for long grades in NC and TN and turns on 40 through the mountains. We have taken 26 through Johnson City to avoid construction on 40--from memory it has some long steep grades. You've got to be comfortable driving the RV on these roads. Definitely stick to Interstates through NC and eastern TN.
