We travel to the Keys each February. We have stayed at Islamorada, Marathon, Little Torch Key and Key West. The best place we have found and keep going back to is Hawk's Cay Resort, situated between Islamorada and Marathon on Duck Key.

Check out their website here:
http://www.hawkscay.com/hcr.asp

They offer all the amenites you could ask for, it's modern, food is fantastic, just an all around nice place compared to the many others we have stayed at.
They have guestrooms and villas, and you can be located waterside, poolside or right on their own marina.
Being centrally located, it makes it an easier stop-over weather traveling north to Key Largo or south to Key West.