2 weeks sounds like a lot, until you start planning, then you find you have to make hard choices! I focused on the ancient sites. I go at a somewhat slower pace than most. I enjoy driving and dislike changing hotels. Here's what I did.
Palermo 2N. Arrived early evening. I spent about 1/2 day at Monreale, the rest in Palermo. On my last day, I took a mid-afternoon train to Cefalu 2N. I returned to Palermo in the morning, picked up some provisions at the market and rented a car. I based in Castellammare del Golfo 3N, went to the Greek temples at Segesta and Selinunte, and visited the coastal towns from Marsala del Vallo to Erice. I spent a day at the temples and archaeology museum in Agrigento and continued to Piazza Armarino 1N. I visited the Villa Romana del Casale and drove to Ortigia 6N (the ancient part of Syracuse). On my last morning I returned the car at the Catania airport.
In retrospect I wouldn't change my itinerary. Ortigia was a delight and I found it easy to drive in and out of to visit other places. I used a day to go to Mt Etna and even though the coast was sunny, Etna was shrouded in fog and that was my only bad/wasted day. I developed a bad knee early in the trip, so I skipped a day trip to Taormina. I had planned to visit Ragusa and Noto, ended up skipping them for more time in Ortigia and not straining my knee. I did drive into Catania to see the WWII museum and it was worth it, even though there was really bad traffic in the city.
Things I learned . . . The small towns close down on Sundays. GPS is good (I didn't have it and got lost more than once). English is not as widely spoken as on the mainland. In Castellammare the middle-aged owners relied on their 16-year old daughter to communicate between us. In Piazza Armarina, I got totally lost and managed to find my B&B thanks to a woman who spoke French. I guess google translate would have worked by that was before I had a smart phone. People were very friendly and willing to go out of their way to help.
