When I first visited Valparaiso a few years ago, I did it on a tour where we stopped at a few wineries along the way. Not sure if that's the best or most appropriate way to do it, but it was included.
That said, it's easy to get to Valpo on your own by bus from Santiago, which I did with my partner last year. We then picked up a great walking tour in town - much better than my private guided tour from a few years ago.
If you can swing it, I'm more partial to Argentine wine and Mendoza, the heart of the Argentine wine industry, is only 90mi away as the crow flies (so long as that crow is able to fly 23,000' above the Andes). It's a 40-min flight if that somehow fits into your schedule. I've always wanted to try the bus ride over the Andes, which I've heard is breathtaking.
ETA: Just noticed the bus thread for Santiago/Mendoza is at the top of the Argentina forum:
http://www.flyertalk.com/forum/argen...argentina.html