Zadar has a very nice historic district with a couple of contemporary monuments along the shore. It's a good stopover between Istria and Split (or Zagreb and Split).
I suspect even nature-haters would enjoy the Plitvice Lakes National Park if they had no significant mobility issues and could manage to see it when it wasn't overrun, so I'll just mention that consideration. The trick is to spend the night before the visit very near the park so you can get there very early and have some time before the day-trippers arrive. For non-outdoorsy people it would definitely be a disappointing destination when mobbed.
I like Zagreb a lot, too. It has a very interesting (partly hilly) historic district, plus quite a lot of good museums, mostly in an area near the historic district. Just ignore the sprawling modern city.
As someone else mentioned, Ljubljana, Slovenia can be combined with a trip to northern Croatia. Ljubljana is very nice, with the old town built along the banks of a small river. There's interesting architecture and some worthwhile museums. It has quite a different feel from Zagreb and is smaller.
Istria is much easier to visit with a car, so I'd take advantage of having a car and include Istria in the trip. Be sure to see some of the historic towns in the interior (like Motovun and Groznjan) as well as the coastal resorts (like Rovinj, Porec and the much smaller Vrsac).