I’ve spent a lot of time in that region, though it’s been a few years. I’d suggest staying somewhere in the central area. There are tons of wineries all along Seneca, Cayuga, and Keuka Lakes, as well as Canandaigua. At the northern end, Canandaigua, Geneva (top of Seneca Lake) and Seneca Falls (top of Cayuga Lake) are all nice small towns with easy access from the NYS Thruway. If you go to the village of Canandaigua, I second Sonnenberg Gardens. Seneca Falls has the Women’s Rights historical sites, if that interests you.
From Geneva, you can drive the length of Seneca Lake down to Watkins Glen SP, one of my favorite places. Watkins Glen and Ithaca are both beautiful- great hiking, waterfalls, gorges. Be sure to wear good shoes for hiking, no flip flops, especially at WG, where the gorge trail is narrow, wet, and slippery, with lots of steps. A nice side trip from WG, about a half hour south is Corning, and the Corning Glass museum.
IMO, Keuka is one of the most scenic of the lakes. Good place to rent boats in either Penn Yan or Hammondsport, both also cute small towns. If you should venture a little west (depending on where you’re coming from) I’d also recommend Letchworth SP for hiking and scenic vistas.