Great thread idea. I've stayed at the Hacienda Santa Rosa, and would echo Vibe Guy's posting - by all accounts, all five of the Hacienda properties in the Yucatan are unique. Santa Rosa was a special place.
Maybe one of the most unusual properties is
Eremito, Parrano - a Design Hotels property in Italy. A small, 12 room property with rooms modeled on the ancient cells of monks, vegetarian food, and dinner taken in silence.
Another option might be
Al Maha, an all-inclusive luxury desert camp in the United Arab Emirates. Sadly, the two Rooms Hotels in Georgia have left Marriott... unique properties in an awesome destination.