We spent 3-4 weeks in Italy/Sicily, our first time there, in December 2012-January 2013. After a pre-Christmas week in Rome, we flew to the Palermo, Sicily airport (which is many miles west of the city), and rented our car there. We headed west, to Erice, then drove counter/clockwise for several days around Sicily, including a quick stop at the Ear of Dionysius cave outside of Siracusa, eventually reaching Taormina for a (very rainy) night. We generally prefer spending several nights in a place, but did one- and two-night stays on Sicily that trip. It was really nice that we were there in the off-season, and it was made clear that other times of the year would’ve been quite crowded,
We took the car ferry from Messina to Reggio Calabria on the mainland, staying in Castrovillari and driving through Calabria, eventually turning in the rental car in Sorrento. After several nights there, visiting Naples, Pompeii, and other sights in the region, we reached Rome by train for our flight home.
Being able to rent from one location and drop off at another made things much more convenient. If you weren’t so keen on covering Sicily north, west, south, and east, you could keep your itinerary more compact. For us, flying round-trip to Rome worked well that trip. Later this year, we’re flying in and out of Naples, but not going to Sicily.
I remember a LOT of stairs most everywhere, but we weren’t specifically looking for limited mobility accommodations. My husband had had knee surgery earlier in the year, and brought hiking sticks for stability that his doctor had recommended, but ramps, elevators, etc. weren’t a prime concern, so I don’t remember what allowances existed 12 years ago, or know what may have been added since then. I do remember that at the temples at Agrigento on Sicily (worth the visit, and we stayed in Agrigento for 2 nights), there was a wide, smooth, paved path, but it was very long. You could, of course, pick where, and for how long, to venture. Many Sicilian towns we were in had steep, and high parts (did I mention stairs?), although the lower town in Modica was level and easier to get around on foot. Rome has curb cuts on many sidewalk corners, but lots of sidewalks are super narrow, sometimes rough, and can have lots of people. I believe that many cities and towns throughout Italy aren’t the most mobility-challenged-friendly places.