A trip from AMS to FRA by car could look like this

1. First day drive to Maastricht or Aachen and stay there the first night there (Both nice towns with a lot of European history)
2. Second day drive to Cologne and spend a night there (Explore the city)
3. Third day drive down the rhine valley to Koblenz (from there you can visit the Mosel valley or rhine valley)
4. Fourth day drive to Frankfurt (Around Frankfurt you can explore Wiesbaden, Mainz and even Heidelberg)

On this route you would skip the Ruhrgebiet which is the most densely populated area in Germany. It might be an alternative to take this route in case you are interested in industrial history and modern art. In this case your itinerary would look like this:

1. First day drive to Essen (a lot of museums and steel and coal industrial museums)
2. Second day drive to Cologne and spend a night there
3. Third day drive down the rhine valley to Koblenz
4. Fourth day drive to Frankfurt.