2 night location - upper / mid keys

Question

We are visiting the keys at end of January. We have 3 days in Key West and then want to spend 2 nights/days travelling through in the rest of the keys, but unsure on best base location. Would you recommend 2 night in one location like Islamorada or Marathon, or 1 night Islamorada and 1 in Key Largo.

After this we will be driving back to Tampa via Everglades.

We have a car and want to visit Turtle hospital, snorkel, visit John Pennekamp Coral Reef State Park and anything else that catches our eye on the slow drive through the keys. Also as it is in 2 weeks should we book this accommodation now or can we just turn up and find a room.

We already have the hotel booked for Key West.

Answer

For a 2-night stay after Key West, your base choice really depends on how you want to structure your driving and activities. Since you have a car and want to explore snorkel spots, the Turtle Hospital, and John Pennekamp Coral Reef State Park, here are some considerations:

Staying in a single location for both nights is generally more relaxing and allows you to unpack once, enjoy the area without moving hotels, and have flexibility for spontaneous stops along the way.

Islamorada: Centrally located in the Middle Keys, Islamorada is a great base for snorkeling, visiting the Turtle Hospital (in Marathon, ~20–25 minutes south), and accessing local beaches and restaurants. Staying here both nights allows a leisurely drive south to Marathon for the Turtle Hospital and local snorkeling excursions, and north for casual stops without switching hotels.
Marathon: Also a good choice if your focus is mainly on the Turtle Hospital, Sombrero Beach, or snorkeling in nearby waters. It’s slightly further south than Islamorada, so it puts you closer to Key West for your recent stay, but a bit farther from John Pennekamp Coral Reef (in Key Largo).
Key Largo: Ideal if your focus is John Pennekamp Coral Reef State Park and snorkeling there, but less convenient for Turtle Hospital or other Middle Keys attractions. Splitting a night in Key Largo and a night in Islamorada can work, but moving hotels can feel rushed given the short 2-night window.

Given your itinerary and interests, a strong recommendation is:

Stay both nights in Islamorada as your main base.
Day trips south to Marathon for the Turtle Hospital and snorkeling, and north for casual stops or diving excursions.
This minimizes hotel changes and maximizes time enjoying activities instead of checking in/out.

Regarding booking: Late January is still a popular travel period for the Keys, especially in the Upper and Middle Keys. While it’s possible to turn up and find a room, availability may be limited and rates higher. Since your trip is only two weeks away, it is strongly recommended to book now to secure a good location and avoid disappointment.

Other tips for your drive back to Tampa via the Everglades:

Allow extra time to stop at scenic overlooks or wildlife areas in Everglades National Park.
Consider short detours for local seafood restaurants along the way.
Check for road conditions or closures along US-1, especially in the Keys.

In summary, Islamorada for both nights gives you a central base, easy access to your key activities, and reduces stress from hotel changes. Book as soon as possible to ensure availability and reasonable rates.