Waypoint Suggestions Between Amboise and Beaune

Auxerre is actually a small city, prefecture of the Yonne department. Very interesting, not many tourists with a lot of restaurants for locals. Noyers is a cute town with a lot of old structures. Semur, though interesting, is getting you beyond the halfway point. One town you overlooked is Chablis, only 14 kilometers from Auxerre. Very pretty with a lot of restaurants.

Unless you're planning on spending your day bashing along the Autoroutes I can't see why you're thinking of going within cooee of Auxerre - that means you're spending the first half of your journey heading away from your destination.

Sancerre is almost exactly halfway between the two, about 2h45 from Amboise, and 3h15 from Beaune (real life timings, not over ambitious route planning timings). The advantage is that you'll see some good scenery along the way, and not have to pay any tolls.

Simon nailed it, Sancerre was my first thought!
Nearby Guédelon castle (a castle built in the past ~20 years with medieval techniques) could be of interest as well.

I was going to suggest Saint Fargeau and a visit to Guedelon in the Puisaye, an hour west of Auxerre.
Saint-Fargeau/Guedelon and Sancerre are on the 4-lane highways and two-lane roads. Auxerre is on the autoroute that goes north and east. Noyers and Semur are beyond the halfway point.

If you are going by Saint-Fargeau and Guedelon, another stop nearby is Colette's childhood home at Saint-Sauveur-en-Puisaye.

But in this area I'd give priority to Guedelon, which I think well is worth a detour. It's fascinating and there's nothing else in France like it.

The advantage is that you'll see some good scenery along the way, and not have to pay any tolls.

Thank You all for the input!

Simon or Bets, would you say the route following the D-976 / D-926 north of Vierzon would be a "scenic" drive? Or would you suggest another way to Sancerre or possibly further on to Saint-Fargeau and a potential stop at Guedelon?

I'd start this way:
Amboise to Sancerre and do this after lunch via Château-Chinon In both cases, the blue route.

Autun is worth a visit, with all its Roman bits