Exploring Douro Valley by car or by boat.

We did the Douro Valley on a wonderful 7 day river cruise.
Seeing the valley by boat is by far the best way to see the wonderful valley. Our cruise included a day trip to see Salamanca, Spain.
Here is my trip report: http://www.cruisecritic.com/memberreviews/memberreview.cfm?EntryID=535267

We used Vantage World Travel and our tour and cruise was cheaper than Viking and had one more day on the tour.
Suggest comparing pricing and itinerary with Viking, AMA, Vantage World Travel, Gate 1 (budget line), Avalon

If you don't want to do the 7 day cruise, you can take a day cruise upriver from Lisbon, but you probably won't see the really best areas.
Our cruise would dock at places like Regua and Pinhao and buses would take us up those curvy highways. You could do this in a car, but do you know what you want to visit. Do you want to visit vineyards, historical places? You need to reserach, or look for tours.

There is a train that runs through Regua and Pinhao upriver on the north side of the valley. That might be an option.

We did a day cruise, the boat and included meal were very nice. However, the scenery is terraced vineyards the whole way which got boring after a while. We took a train back to Lisbon.