My wife and I went to South America in November. I used travelocity to book all of our flights with the exception of one. 
 
We visited: 
- Santiago, Chile (American Airlines flight from Edmonton via Dallas Fort Worth) 
- Buenos Aires, Argentina ( Aerolineas from Santiago)
- Colonia, Uruguay (via Ferry from Buenos Aires)
- Iguazu Falls, Argentina/Brazil (Lan from Buenos Aires booked directly from Lans website)
- Rio De Janeiro, Brazil (Aerolineas from Buenos Aires)
- Edmonton (American From Rio De Janeiro via Miami)
 
I used travelocity's multi destination option to book the flight from Edmonton to Santiago and back to Edmonton from Rio De Janeiro,and just played around with the dates a little to find the cheapest flight. For the other flights we just looked for the best price comparing prices on travelocity, expedia, and south American airlines (Aerolineas, Lan and Tam).
 
 
A few things to note:
 
- You will need a travel visa for Brazil which will cost $72ish.
http://www.brasembottawa.org/en/index.html
- Our flight into Rio was the most expensive flight we booked other than the flights to and from South America, and we found it to be expensive place to visit in general. 
- When booking flights between cities it is often cheaper to book return flights than one ways.
- We used tripadvisor for picking out hotels, only one bad hotel experience (Iguazu Falls).
 
I will add more if I can think of anything.