I first want to say that my driving experience was completely different from the one Cameron posted in his blog. What he described was what we were afraid of, but not what we found. The autostrade were in great shape. Sicily driving was definitely different from US driving, but for the most part, it wasn't difficult or stressful. My friend (who actually did the driving - I did the navigating) later drove in England, and he said driving there was FAR harder than Sicily driving!
That said, I was insistent for Sicily that we had a car with zero deductible. As did some of the others above, I wanted "walk away" insurance - when you turn in the car, you don't have to worry if they find anything (and by all reports, the companies are experts at finding a problem when you return the car!). If you're willing to assume the risk, which as said above can be several thousand euros, you can go with a lower policy.
My other tip is to look at Kemwel. They're under the same corporate umbrella as AutoEurope, but often have lower rates (in our case, much lower, particularly for the zero deductible we wanted).
As for the short drive to the autostrada, in Palermo it's not hard. We rented from Hertz; the next year my friend went back, and his car (booked through Kemwel) was from Europecar. They're in different locations in Palermo, but in neither case do you have to drive through the congested old center to get out of town.
Note that when he returned his Europecar at the Catania airport, they insisted on going over the car fully, even though he also had zero deductible insurance that time; this delayed his getting to his plane (he made it, but with much less time than he liked). Hertz at Catania airport was pretty quick.
For more on my trip, including lots of details on driving, here's my trip report from 2014 (warning - it's long, so you can feel free to skip down to the driving sections if you wish): https://community.ricksteves.com/travel-forum/trip-reports/sicily-palermo-caltanisetta-siracusa-taormina