We limit our overall trips distances to 3000 miles or less to avoid having more time sitting behind the wheel then in enjoying time at places along the way. That means roughly 1500 miles or less from our house.
For greater distances we either fly and rent a car and stay at hotels and B&B's, or we fly and rent an RV. We arrange to arrive in a town early in the morning and the day we land we pick up the RV, stock up on supplies, and are on the road. Coming back we arrive the afternoon before we plan to fly home and stay at a hotel with airport shuttle service.