To save time, money and the hassle of air or train travel (with connections) from Salzburg to Prague, my husband and I are considering driving a rental car on a Sunday in August. Can anyone suggest a car rental company that will allow a one way trip? Where does one easily drop off a rental car in Prague? I sure don't want it in the city. Thanks.

I don't think you'll save money since the drop off charges will be very high. I'm guessing at least $500 but you can confirm this with any car rental company. A friend paid $700 last year to drop off a car in a different country.

The Prague airport would probably be the easiest location to drop off the car.

Contact AutoEurope, a consolidator, for rentals.

On the trains you change twice, once in Linz, once in Cesky Budejovicka. When I did this, we just had to walk across the platform at Linz and a platform change at Ceske Budejovicka. Not difficult unless you have a ton of luggage. Considerably less difficult than navigating your own way from Salzburg to Prague airport. For timetables go to http://jizdnirady.idnes.cz/vlakyautobusy/spojeni/ in the bottom right hand corner there is a link to turn the site into English.
And as has been mentioned, it will be a LOT cheaper. You can even enjoy the Austrian and Czech countryside as a chauffeur (train driver) takes you to the centre of Prague.
http://www.jeremytaylor.eu/prague_photos.html

Google Mike's Chaueffer Service. They are located in Prague and do transfers to/from other cities. Mike picked us up in Vienna and transported us to the door of our hotel in Prague for a very fair price. You might find out you can really remove all the "hassle" of this transfer by using Mike. I highly recommend him.

Mike is driving us from Prague to Salzburg in two days. The cost is 6200czk. For an additional 600czk, we are breaking up our trip with a 2 - 2.5 hour stop at Ceske Krumlov. Much pricier for two people than a train, but also much more relaxing, and maximizes or sightseeing time on a relatively short trip.

Incidentally, we also used Mike's service for an airport transfer. The cost was 550czk. My experience so far with Mike's service has been very positive.