I live in the Key's, if that means anything, and these are my recomendations.
Stay at the Pier House or the Marquesa.
Eat at Michaels, 7Fish and
El Ciboney (for local Cuban food).
If you're partiers, and most KW visitors are, do the Duval Crawl.
Do visit The Hemmingway House and do the oh so hokey Conch Tour Train.
Grab a drink at the Schooner Wharf and The Green Parrot (real KW) ... The Parrot has great musical choices.
Visit the Garden of Eden Bar if you're crazy enough to go to a real clothing optional BAR!
Have fun.