You can take a bus from almost everywhere in Chile, there are many companies, like: Tur Bus (in the pic), Pullman Bus, Tas Choapa, Libac, Lit, etc...
If you're in Santiago and want to visit Santa Cruz, you can take a bus here, at the Bus Station in Alameda (metro station Universidad de Santiago), and take a bus to Rancagua or San Fernando first, and then another to Santa Cruz.
Is very easy and prices are reasonable.
A rental car is a really great way to get around especially outside of Santiago. My friends and I rented a car and off we went. The roads aren't really well sign posted unfortunately but it is pretty hard to get lost!
It cost us about 215,000 pesos for 4 days.