I used to live near Frankfurt (Darmstadt, actually). I always recommend a trip up the rhine, toward Koblenz (starting around Rudesheim/Bingen on the B9), and then, at Boppard (2/3 way to Koblenz), or around there, head west to the Mosel river and make your way back down south...beautiful views, great castles all along the way...there is a twin towered castle called Thurant, I believe, near Boppard (but it might be near St. Goar...). Once to the mosel, I find my way to the B49 and follow it over the bridge onto the west side of the river. Make a stop at Burg Eltz if you haven't been there (the true fairy tale castle from middle centuries) and then you can stop all along the Mosel at various winemakers as you head south. Tough day trip, quite frankly, but I've done it 3 different times. Or you can make a night out of it and head all the way to Trier. Or just do the Mosel part, but will miss some great castles on the Rhine side (although, there are plenty of decent ones, not least the Eltz, on the Mosel).
Just my 2 cents, and I could be more clear if you think you're interested.
Oh, and another note on a GREAT restaurant known for fine wines...Schloss Rheinhartshausen between Wiesbaden and Rudesheim. Their Restaurant Prinzess von Erbach is outstanding and featured from time to time as one of the few grand award winners of Germany in Wine Spectator's magazine. Not cheap, by any standard, though, but probably one of the most memorable dinners I've had in my life. Worth the trip to the area for just that, and their wine, and easier timewise than the whole river tour. Link below to the restaurant site:
http://www.schloss-hotel.de/en/home/index.htm?folding=1