Gaslamp Quarter: Located in a 16 block area, this is a downtown district with many old Victorian buildings. There are many boutique hotels, restaurants, clubs, theaters and retail stores. It is one of my favorite areas and well-worth a visit while you are in town. I had not been there in several years.
I also checked out the Andaz San Diego hotel which is an attractive, chic and contemporary property which has a roof top bar and pool with great views of downtown that reminded me a lot of the Standard Hotel in downtown LA.
Another great hotel option if you want to be in the center of the Gaslamp Quarter, is the The Keating. If you want activity, food and nightlife you are staying in the right spot. For lovers of the more traditional, The US Grant hotel might be the place for you. It is at 326 Broadway.