From the World Heritage inscription:
After the arrival of Christopher Columbus on the island of Hispaniola in 1492, Santo Domingo became the site of the first cathedral, hospital, customs house and university in the Americas. This colonial town was laid out on the grid pattern that became the model for almost all town planners in the New World.
The first impression of the Spanish colonizers was favourable: the nature was luxuriant; the aborigines were friendly, and it seemed that the ground was rich in gold. Using what was left of the Santa María, Columbus built the fort of the Nativity (Navidad) on the northern coast of the island not far away from a peak that he called Christi Mount, leaving 39 men there under the protection of the village head. When Columbus returned to Hispaniola a year later, the fort had been destroyed, his men were dead, and the aborigines had become mistrustful. He founded a new colony further to the east, which he called Isabella, and left it under the control of Bartholomew. However, the first revolts were very soon to begin.
In 1496, Bartholomew abandoned Isabella in order to move on the southern coast of the island, where he established the settlement of Nueva Isabella, now Santo Domingo, on the left bank of the Ozama River. Because of the insurrections that continued to upset the island, Columbus was replaced as Viceroy and Governor of the colony by Nicolás de Ovando. In 1502 a typhoon destroyed the city and the fleet that was preparing to return to Castile. Ovando decided that the city should be completely rebuilt on its present site on the Ozama.
This colonial town was laid out on the grid pattern that became the model for almost all town planners in the New World. The city was to be embellished with a cathedral, a hospital, convents, a fortress and a university. At that time it was not appropriate to describe these buildings as having been built in the colonial architectural style because they were all based on plans that faithfully followed models imported from Spain. Earthquakes and pirate attacks were in due course to ravage the main buildings of the city, such as the convents of the Dominican, Franciscan and Las Mercedes, the three religious orders that pioneered the evangelization of the New World, and the Hospital of Nicolás de Ovando.
Among the most outstanding buildings, the cathedral was constructed between 1514 and 1542; it is the oldest in America, and is one of the architectural wonders of the Colonial City. The main entrance stands next to the Columbus Plaza, where stands a giant statue of the great navigator himself. The fine stained glass is by the famed Dominican artist José Rinçon Mora.
The Ozama Fortress and Tower of Homage were built in 1503: this stone group is said to be the oldest formal military outpost still standing in America. The Tower of Homage still stands in the centre of the grounds, an impressive architectural structure that is medieval in style and design.
Santo Domingo is the oldest colonial city in the western hemisphere, which in and of itself is probably reason alone to be place on the world heritage list.
Santo Domingo is pretty easy to visit. The colonial zone (aka the old city) is right where cruise ships dock. It is also the location of a large cluster of the tourist hotels in Santo Domingo.
There are two parts of the old city that I would recommend. The old fortification (seen above) still has parts which are standing. This is what originally guarded the harbor. I’d also make sure to visit Christopher Columbus Square, which is the heart of the old city. Here you will find many cafes, restaurants and the cathedral.