It depends what you are willing to spend, although if you get a good price for your dollars then the hotel will be more affordable.
The more expensive hotels tend to be in the Altamira, Las Mercedes, La Castellana area. Near these you have shopping malls, plazas, bars, restaurants, etc and it is fine to walk around by day. I would suggest travelling in official taxis only if you wish to go out at night. The San Ignacio mall is your best bet at night - there are shops, cinema, bars and clubs.
If you are looking for budget options try around Sabana Grande and near to the University, although don't go walking in this area at night. By day you have the El Recreo shopping mall and Boulevard that can be explored, or take the metro to the Altamira area or west to the historic downtown area, although that area is best to go with someone that knows the area or with a good map.
Edited: 10:53 am, December 18, 2010