Need help please planning a 6 night itinerary flying in and out of Frankfurt!

Considering you are in Frankfurt and have a car take a tour of the Romantic Road. Here are details of points of interests
http://www.romanticroadgermany.com/

The Mercedes Museum at Stuttgart is about a 2 hour drive south of Frankfurt.

"Rhine River, Castles and beautiful scenery..."

The Upper Middle Rhine Valley is the best part of the Rhine and has what you seek. You can tour castles in BRAUBACH (Marksburg Castle - medieval, intact) and in ST. GOAR (Rheinfels Castle, ruins + museum.)

Map showing Bingen-St. Goar segment, good for cruising and sightseeing - this segment shows you the best scenery in 1.5 hours. Be sure to cruise Bingen - St. Goar; St. Goar - Bingen will take nearly twice as long because of the strong Rhine current.

"...was thinking it may be best to stay in bigger cities."
That's not always the best plan... many of course were destroyed in WW II and rebuilt so you will necessarily give up some old-world charm in these places. For the Middle Rhine Valley, Mainz and Koblenz are large and would meet your needs; Koblenz would place you close to the Mosel and the Lahn rivers for additional outings. I have stayed nearly everywhere - the smaller towns of St. Goar or Boppard might be good base towns for you. You'd be about 15-25 minutes from Koblenz by train if you want to hit the big city, and trains run very late into the evening (22:52 or 00:03 from Koblenz - good to know if your evenings include alcohol.)

Both Boppard and St. Goar are nice towns and on the same side of the river with the other more interesting towns (Oberwesel, Bacharach.) All these small towns are very close to each other on the same train line. If you stay in St. Goar or Boppard, you will have a car/passenger ferry (like this one in St. Goar) at your disposal for crossing the river - there are no bridges between Koblenz and Mainz. (Boppard has LOTS of accommodations choices and places to eat - people do linger there in the evenings in summer and it may be enough action for you.) The two places of interest on the EAST bank are Braubach and Rüdesheim; if you use the trains over on that side, St. Goar's ferry will put you near the train station across the river in St. Goarshausen so you can get to those places.

Cruising: You will need to use the train before your cruise to reach Bingen, then your cruise brings you back home to St. Goar. If you stay in Koblenz instead: you'll need to use the train from Koblenz to Bingen and then another train after the cruise to get back to Koblenz from St. Goar. (There actually are a couple of boats that go all the way from Bingen to Koblenz but they add a lot of expense and time to the cruise (it's 4 hours,) and the scenery as you approach Koblenz really isn't worth the extra time + €.

3-4 nights for this area is about right.
Oberwesel
Bacharach
Boppard - chairlift and Gedeonseck

Thank you for the responses. We think renting a car would be best. Do you think something like this is doable in the time we have?

Day 1 - Arrive in Frankfurt in evening - check in, relax and dinner
Day 2 - Frankfurt - Rhine River Cruise
Day 3 - AM Drive to Stuttgart for Mercedes Museum then on to Munich
Day 4 - Munich/City Tour or Dauchau?
Day 5 - Munich Area/Day Trip to Castles?
Day 6 - AM Drive to Rothenburg or Nuremburg to spend last night
Day 7 - Drive to Frankfurt Airport for evening departure

Sort of want to make a loop but a little more focus on Bavaria just not sure which way would be best to start and end.

"Do you think something like this is doable in the time we have?"

Did you check the mileage? It's 1200 km or more. If that seems to you doable over 6 days and that's the sort of experience you want - one where you hit a maximum number of specific, big-name tourist spots, then you can surely do that... but understand that you are simulating a rapid-fire bus tour. What happened to "2 nights in 3 cities"?? You have 5 different overnight stops.

You want a trip with "a little more focus on Bavaria" but IMHO 6 days are insufficient - it would be the same if you were to visit only Bavaria. But that's what I suggest you try to make it less of a driving frenzy. Skip the Rhine - just going there for a cruise is basically skipping it anyway. Also skip Stuttgart (do BMW in Munich.) FRA isn't the best airport for Bavaria but it's not too far from the Bavarian town of Würzburg, on the Romantic Road, or from fabulous Miltenberg, also in Bavaria. From Miltenberg it's only an hour's drive to FRA - so maybe you wouldn't need to overnight at FRA (boring) at all. Go there on night 1 and return there on night 7? Then you'd have your 3 nights in Munich and maybe 2 nights in Nuremberg or Rothenburg (or in between somewhere and do day trips.)

Unless you just want to hang out with tourists, I would urge you to reconsider the ultra-touristy destinations of Rothenburg and Neuschwanstein (which is a late-19th-century palace, not a real castle.) As Miltenberg demonstrates, there are lots of great places in Germany without the international tourist trappings. Iphofen is another - and it might be a good base town for Rothenburg and Nuremberg as well. Coburg Castle is a good replacement for N'stein, and Bamberg is a fabulous old place.

I apologize if my last response wasn't clear. The intention was to spend 2 nights in frankfurt, 3 in Munich and 1 in Rothenberg. From the map searches I have done it appears that the distance between Munich and Rothenberg is approximately 2 hours and again between Rothenberg another 2 hours back to Franfurt airport. It didn't seem like a driving frenzy. We would not stay another night in frankfurt at the end as we would be flying out that evening. We are only using frankfurt due to the fact that we are able to fly direct from new orleans there with no stops. I will reconsider taking the Rhine portion out and perhaps just going straight to another destination in Bavaria right after we land.

"I apologize if my last response wasn't clear. The intention was to spend 2 nights in frankfurt,"
No need to apologize - I read 2 nights as well but one on Night #1, a Rhine night on Night #2, and wrongly assumed another Frankfurt night on Night 7 - (my error.) And I think I assumed a night in Stuttgart as well - I reckon the 5+ hours of driving Frankfurt-Stuttgart-Munich simply did not compute.

So if I read your plans accurately, you actually have one night less than I thought and with your plan, even more total miles to drive (since you're driving Frankfurt-Rhine-Frankfurt on Day 2.)

"I will reconsider taking the Rhine portion out and perhaps just going straight to another destination in Bavaria right after we land."
Yes, I'd still go with this strategy.

Here's a plan that with options that gets you into just 3 cities for overnight stays and gives you castle, palace, and river cruise options. Still a lot of driving for the time you have but perhaps doable...

Day #1: Würzburg (northern Romantic Road, good base town) for night. (Not a long drive if you must drive this day. But I'd take the direct train from FRA for safety after an international flight / possible jet lag, then pick up the car on the morning of Day #2.)

Day #2: Choices...

• Day trip to Bamberg and Coburg (castle.)
  
• Day trip to Rothenburg + the Main River towns of Ochsenfurt, Sommerhausen, and Marktbreit, all on the way.

Day#3: Check out. Choices...

• Morning: City walking tour of Würzburg in English if available on this day, 11 am. OR: river cruise to Veitshöchheim
  
• Afternoon: See Residenz Palace.

Night #3: Drive to Munich for night.

Day #4: Munich sights (Nymphenburg Palace? BMW? Other?)
Day #5: Dachau, Munich
Day #6: Check out. Choices...

• Munich a.m. sights + drive to Nuremberg in p.m. for night
• Drive straight to Nuremberg for day, night (if you have lots of sights in mind there.)
• Munich a.m. + drive straight to Stuttgart for day, night

Day #7:

• Check out of Stuttgart. Drive north along the Neckar River to Heidelberg and/or along the Bergstrasse route to FRA
• Check out of Nuremberg. Drive to Iphofen and then west via Würzburg to Wertheim, Miltenberg, and on to FRA.