I agree that Belgium is a very rich destination that will reward the time spent there. Your OP sounds like a request for "a B&B in the Costswolds." I don't know if there are any such villages in Belgium. Certainly the bigger the place you base, the worse the morning auto traffic will be. Although Brussels has many historic sights, it doesn't (opinion) have a lot of charm. Antwerp (a nearby example) does, despite being a big city with a lesser case of Amsterdam's ills.
As a previous user, I would suggest that you buy Lonely Planet Belgium, because it goes into so much detail about each city it covers. For example, it says (using U.K. terms), partly metaphorically, (I haven't been there ... ) that Dinant has the aroma of stale french fry grease! (That's a comment about bus tours coming to see the citadel on the cliff.) I have daytripped by train from Antwerp a lot, but we also spent three nights at a luxury manor hotel, La Butte aux Bois. That was expensive, and I'm not prepared to recommend enthusiastically. We chose that location (we like to move every three or four days) to see the medieval centers like Tongeren and Tienen, as well as the Bokrijk open-air (old building) museum. We then spent one night in Leuven before flying home from BRU, which is a very attractive university town, and close to the airport. But it's not a village. I am not an expert, but while there are many lovely medieval town centers with cathedrals, I suspect there is no "Cotswolds" in Belgium! There are plenty of residential developments with (real) thatched roofs, but they are all modern replicas.
We did not have time to hit Maastricht, Netherlands on that drive, but I often read good things about it. You haven't mentioned any of the interesting stops between Amsterdam and Bruges, like Leiden, The Hague, Rotterdam, the Delta Works project. Although I will admit that we drove from Cologne to Amsterdam on our "Netherlands" single-country trip, I really don't think of Amsterdam as being next to the area you are asking about. Highway driving just isn't that interesting.
I have read that there are some attractive (and hilly) hiking destinations in Southern Belgium. But I'm not familiar with them. Dinant strikes me as too much of a commitment to the South unless you are interested in these outdoorsy parks. I recommend that you do not try to include Luxembourg from a Belgian base.
When you choose your destinations, keep in mind that the reason so many people worship Bruges is that it is so substantial and charming a medieval center. It is possible that you don't need to see every medieval center, surrounded by postwar reinforced concrete development, in the country. To put that another way, I often write here that Gent has 70% of what Bruges has, with only 10% of the tourists. Another helpful thought might be that at one time, after the cloth trade declined, Mechelen was the third largest city in Europe. Today, it is an attractive half-day train outing from Antwerp or Brussels-It's so nice I've been there more than once. But it's a small city. It has the "ghost" of a Beguinage, with the original street layout, and some historic stones set in the walls. But most of the buildings are modern. Most posters on TripAdvisor are asking whether the brewery has tours!
Edit: Because you are interested in something like off-the-beaten path, and your trip is in September: Find out Open Monument Day in both the Netherlands and in Flanders/Belgium. You won't find the 2015 attractions listed this early, but maybe you can see if any of the 2014 lists included anything that interests you. (These skew urban rather than rural.) These lists tend to be easier to find in Dutch, but there's always Google Translate.