Perhaps one of the most charming homes of colonial Santo Domingo [1], the Hostal Nicolás de Ovando (Las Damas at General Luperón) was built in 1509. It was the home of Governor Nicolás de Ovando, who is responsible for choosing the site on which Santo Domingo was built (after it had been destroyed by a hurricane in its original location).
Christopher Columbus was often a guest of this home, and you can be too. It is now a luxurious Sofitel hotel [2].
Links:
[1] http://www.moon.com/destinations/dominican-republic/santo-domingo
[2] http://www.moon.com/destinations/dominican-republic/santo-domingo/accommodations/ciudad-colonial