Going to Germany for the First Time - Need Suggestions

Young children travelers have special needs and they can get pretty tired due to all the walking required. I suggest your family travel as absolutely light as you can with luggage, etc.--following Rick Steves' packing list and using rolling bags.
You can take a train into Munich and use public transportation getting around town. Upon leaving town, you'd do better with a rental car going over to Salzburg, down to Innsbruck and around. You can just travel more efficiently with the rental car and see so much more. You can also travel on your family's time--going and coming and stopping when needed.
Bavaria and Tirol are very easy places to travel through with good roads, incredible mountain vistas and reasonably priced accommodations. We just love to get out and ramble from village to village up on the mountainsides. And there's just so much to see everywhere you go.

David's concern about lots of walking may apply within Salzburg since you won't have a room there for rest breaks. It does involve a healthy amount of walking unless you use public transport. But then you cannot really drive easily within Salzburg either. I'd use the train. You can get there in less than 2 hours by direct regional train for €31 with a Bayern (Bavaria) Ticket day pass - and return to Munich as well (gas alone would be €40+.)

"...we're pretty open to what we see and would love some suggestions."

In between Frankfurt and Munich is the region of Franconia ("Franken") in northern Bavaria. Franconia is well known for its regional cuisine and its many wineries and small breweries. It's a scenic area with varied landscapes and some very fine old-world towns, one that many visitors rush right past (with the exception of tourist-magnet Rothenburg of course.) And IMO that's a shame.

Würzburg, Nuremberg and Bamberg (itself a UNESCO World Heritage site) are the 3 cities of note; smaller places of interest include Rothenburg, Iphofen, Bad Windsheim, Sommerhausen, Ochsenfurt, Marktbreit. Würzburg is only about 1.5 hours from FRA airport by direct train, and you have to pass through it to get to Munich anyway. It's a major train hub and would make a good base town for a few days at the beginning of your trip. All the other places are within an hour's train ride.

Würzburg highlights
Rick on Würzburg
Railway map of the Würzburg area

Bamberg
Iphofen (wine town)
Sommerhausen, Marktbreit, Ochsenfurt
Bad Windsheim's Freilandmuseum (outstanding exhibit of historical buildings and more)
Nuremberg

Because you're in Bavaria here, you can use the Bayern Ticket for outings to these places. Just buy it at the station. All but Sommerhausen have train stations (there's a bus connection to Sommerhausen, I believe.)

If considering a daytrip to Salzburg from Munich, then I agree a train is a better option. Driving into, out of, or through Munich, quite simply, is not a fun experience. The Autobahn connection between the two cities (A8) does offer amazing scenery, but it's also very famously congested. Expect to crawl very slowly for long portions of the trip if you drive. Although parking is easy to find in Salzburg, you would explore the city on foot anyway, as the area of interest to tourists occupies a surprisingly small area. I would say that if your son can manage to walk around a large shopping mall, he shouldn't have trouble in Salzburg...whether or not he'll find it interesting is probably another matter.

Munich has a very nice zoo, and for some reason, it never seems to be particularly crowded. I'm sure the 5 year old would enjoy it.

All but Sommerhausen have train stations (there's a bus connection to Sommerhausen, I believe.)

Yes, there is a bus, leaving from Würzburg Hbf. Besides, it's a short walk over the Main bridge from the Winterhausen train station (on the Würzburg - Ansbach line) to Sommerhausen.

Bad Windsheim's Freilandmuseum (outstanding exhibit of historical buildings and more)

BTW, the historical center of B.W., if tiny, is worth visiting too. And beer and food at the tiny Doebler brewery are great (http://www.brauhaus-doebler.de/index.php?id=4).

As grandparents with a "five-ish" one to entertain in Germany, we've normally operated around Bad Durkheim & the lower Western edges of Germany to do so. An easy adult / child day trip is a Rhine cruise out of Mainz which is immediately south of the Frankfurt airport. The whole area there could be a good first stop to get acclimated to your German adventure. The boats have decent (nothing fancy) eating facilities with good places to rest a child, if needed. We've done this. The Rhine cruise would start and stop from Mainz, then you could get going on the excellent recommendations of the other contributors. I would also say that Germany is sprinkled with many amusement parks and centers generally like those in the USA. You can easily find them online and one may be a quick fix for an antsy youngster that needs to run off some energy.

I would start out by having him eat German food, Bratwurst, Knockwurst, Wienerschnitzel, potato balls, etc. You can find Wienerschitzel at almost every restaurant so he will have something he can eat. We did this for our 7 year old before her first trip, she was a picky eater, but loved German food. Prepare him before trip by taking long walks with him. You will have to reduce the number of places you will see every day because he will be tired. We tried to stay central to sites. We would start early, head back for a rest around lunch and then go back out later. Every few days we would stop by a park for her to play.

Try to stick to trains as best as possible, your son can get up and move around during train rides.

Find a salt mine to go visit. Kids tend to love those.

If you are in Frankfurt and they are running when you are there, a tour of the city on the river would be fun. It's a great way to see the cityscape and my 5 year old enjoyed it last year. Munich has always been a favorite city and I'm excited that we are heading back about the same time you are. The Munich Zoo is awesome and my 5 year old is excited to go back while we are there. She remembers the meerkats and rhino. The English Garden is a great place to go on a beautiful day to let him run around. There is a playground by the beer garden and Chinese Tower and the Isar river runs through it. If its warm/nice out its a great place to have a picnic and if you can find a Euro store or place that sells a ball he could really have fun. The Viktualienmarkt is a great place if he loves fruit. My daughter loves all fruit and her eyes always light up when she sees all of it, she has a hard time picking out what to get to snack on. Plus there is a stall there that sells really good ice cream. She also loves to watch the clock (the name is escaping my mind at the moment) in the Marienplatz when the figures are going around. An awesome day trip from Munich is going to the Zugspitze, the tallest point in Germany. Its a beautiful and easy train ride. You then get onto one of the cog trains and either ride it almost all the way up or ride it to the gondolas and then go up. Beautiful views, you can step into Austria while you are up there. My 5 year old loves looking through the telescopes they have.