The first two things you'll notice flying into Santiago: 1) The incredible Andes, including Aconcagua (if you're lucky), and 2) the horrible pollution. Unfortunately the pollution is a fact of life in Santiago throughout the warm months.
The neighborhoods of Las Condes, Bellavista, and Providencia are beautiful places to stay, with resturants, nightlife, shops, arts fairs, and accommodations. I stayed downtown, which was a little bit of a walk to get to any of the entertainment districts. The city parks (Cerro San Cristobal, for one) are good and central places to get away from the traffic and noise.
Quick Tips:
As mentioned above, downtown is not the most exciting place at night. Be sure to visit the mercado central - you find original art, cheap t-shirts, leather, clothes, postcards, and all kinds of other knick-knacks. When I was there, however, I say very little in the way of Mapuche arts and crafts; if you're looking for Mapuche items and lifestyles, you'd better head south (at least to Temuco.)
Best Way To Get Around:
You'll need to take a minibus from the airport to the city - the airport is at least 30km from the city center. There are frequent and inexpensive buses that will take you to the main bus station, which is right on the subway line. The subway is clean and safe; you'll find it very useful for getting around the city. The cabs were clean and comfortable.