I'm wondering if anyone can make a recommendation on how to spend an airport layover in Dusseldorf. We will be returning from a Meditterranean cruise on Sat Sept 18th and due to Freq Flier ticket restrictions, must spend the night in Dusseldorf. We have a hotel at the airport, but would like to make the most of the time by seeing something other than the hotel and airport. We arrive 2:45pm and depart the next morning at 10am. Is Amsterdam too far by train?

Amsterdam, 3 hours, too far. Just hop the S-Bahn, go downtown, stroll the pleasant river front, perhaps take a Rundfahrt (boat cruise to nowhere) on the Rhine and head to Dusseldorf's Latin Quarter for a meal - very animated in nice weather and on weekends - many outdoor cafes, etc. Or try a typical German beer hall, or shop Dusseldorf's fashion alley - right up there along with Milan and New York I guess, though not into fashions. Or hop a train to Cologne (30 mins 2 trains/hr) to see the world's largest Gothic cathedral (next to the train station) and stroll its pleasant riverfront walkways.

I second the recommendation for Cologne.
Amsterdam is 2 hrs 13 minutes by ICE.

Enjoy Dusseldorf! It has an excellent art museum, a lively old town, some good restaurants. We had a fun meal at the Schlosser brewhouse/restaurant.
If you really want to get out of town, don't plan on going so far away. Hattingen, a pretty medieval town, is a short hop away by train or bus. The old town is full of 16th century half timbered buildings, some nice shops, cafes (like the Cafe Harlekin, in an old schoolhouse that dates back to 1517), restaurants. But as much as I like Hattingen, don't make yourself nuts...stay in Dusseldorf!
When we lived near Dusseldorf last year, I made many trips to the airport on the S-bahn. It's very easy to use. At the airport station, though, don't forget to stamp (validate) your ticket in the little machines.

Yeah, enjoy the pub scene in Dusseldorf. There is one next to the other in the old town, and it gets very very lively at night!