We've had two classics.
First, when DS was young was Florida, including Kennedy Space Centre, Busch Gardens, Alligator air boat ride in the Everglades, Mermaids at Tarpon Springs as well as the usual Orlando theme parks, particularly Epcot, MGM and the dolphins.
Second, when he was older, was a California road trip, starting in LA, then down to Dan Diego, over the Mexican border to Tijuana for the day, then across to Flagstaff Arizona, then Grand Canyon, then Las Vegas, then Death Valley, Yosemite National Park, finally ending up in California via Napa Valley wineries and trip to Alcatraz.
Nothing else has ever come close. Well except Canada, doing the boat trip under Niagara Falls, then Toronto, Algonquin National Park and up to Ottawa, thousand Island boat tour and on up to Montreal.