I had seen pictures years ago, of a crazy road with all kinds of switchbacks that crossed the Andes, and always wanted to see it.
Many North Americans may have a connotation of buses that is vastly different than the reality in other parts of the world. Well, like most things, it depends on price range: you can get remarkably far for a couple bucks (which is still a fine way to travel on a budget), but you can also get a very comfortable, near-luxury experience in buses for longer distances for a fraction of the cost of an airline ticket or renting a car. And in any case, the bus system in both Chile and Argentina are part of a public transportation infrastructure that is vastly superior to the Third-World public transportation in the United States.
With many different options, we went with Andesmar, which had double-decker buses with fully reclining seats for just over $30/pp for the ~7 hour ride, and was known for having a good safety record. You could do this ride overnight and save daylight as well as a lodging night, but he gorgeous views from the 2nd level especially were worth the price of admission. You also get coffee/tea and a meal, as well as a movie and/or obnoxiously loud Latin American music videos, for better or worse.
And it costs the same as taking a shuttle one-way from Fort Collins to DIA.
On the Argentina side, I found the Uspallata Valley to be incredible and worthy of more exploration as we went through, but we continued on to our equally beautiful destination in the Mendoza region.