Your best bet for getting to Key West with the least hassle is to fly Delta and connect in Atlanta nonstop to Key West. I like to fly as early in the day as possible, in case you miss a flight and need to catch a later one. Atlanta has at least one really nice Delta Crown Room, a must when traveling with little kids. But a fun way to go if you have some time and are not traveling safari-style with the kids is to fly Jet Blue nonstop into Fort Myers, rent a car, and make what can be a pleasant, sunny drive down through the keys.
If you are rushed, hate driving, or are on a tight schedule, I’d opt for plan A. If not, there is some fun to be had driving down the keys. You’ll head south from the Fort Myers airport and pick up Route 75, which turns east and becomes what locals refer to as Alligator Alley. You’ll drive east in fast-moving, easy traffic to the Florida Turnpike, which will take you south to Florida City, a tacky highway intersection. Here you will simply continue on into the Florida Keys. You’ll come to the Marriott Resort in Key Largo. At that point you will have driven a not-too-stressful three hours or so. If that’s enough for you for the day or you are already going to be running into the mid-afternoon, I’d book ahead for a night at the resort.
Your next move will be to continue your drive down A1A. At mile marker 81 or so, you will come to the huge World Wide Sportsman. It will be on your right, flying a huge American flag out front. You can’t miss it. If you like fishing, you will have found your Mecca. If not, you’ll still enjoy fish sandwiches on the dock, and a great fish store is at hand if you need some fish to go. On the way down the Keys, you can have fun at Theatre of the Sea, Looe Key National Marine Sanctuary, and John Pennekamp Coral Reef State Park. Bahia Honda State Park offers probably the best of a very weak group of Keys beaches. Quite honestly, you’re not going to the Keys for the beach. The best place for lunch in the lower keys is the Square Grouper at about mile marker 22.5 on Cudjoe Key.
From there you will coast on into Key West with nary a stir. I hope you will not get hung up in an A1A traffic accident. These things do unfortunately occur more than any of us would like. Just get out a book, crack a cold beer, and wait it out on the beach like a conch. Have a great time in the keys. And oh yes, when you hit Tavernier just south of Key Largo, on your left will be the Tavernier Hotel, made famous in song by Jimmy Buffett.