Haven't for that purpose, but have rented a car to go visit grandparents who live a couple hours away. DH got picked up at our resort (think it was the Contemporary) and shuttled to car rental, then came back and picked us up
We did our last trip. Super easy. We were at HS and took the boat over to the Dophin. I think if you rent from the Car Care Center, they will pick you up from your hotel.
On our last trip we split WDW into two segments and visited my sister's family down in Hollywood, FL (north of Miami) in the middle. We rented from National at the Dolphin and it was easy.