This will obviously depend on personal tastes. There are many fine art galleries and historic buildings. Union Square train station is a favorite photo opportunity for tourists. I would recommend stopping into the Wynkoop Brewery on the corner of Wynkoop and 18th street for a meal or at least to sample one of their tasty brews.
Many pubs have specials on certain nights.
If staying in one of the downtown hotels, you re better off moving around on foot, as the price of parking is outrageous and everything is within a short stroll. There are free shuttles that run up and down the 16th street pedestrian mall if you are planning on checking out the shops in that area.