South of Rome

Sicily alone will take the whole 2 weeks. Why don't you fly to Sicily, rent a car, and visit it the whole time. Not too many tourists in October, and certainly not too many from the US regardless of time of the year.

If you stick to the mainland only, you may want to look into Apulia (Puglia) and the city of Matera (technically in Basilicata), which is at the heel of the Italian boot, in addition to the Naples area (Ercolano included).

You can't do Sicily and the southern mainland in two weeks. Sicily is too huge and too many things to see. It's a vacation on its own. Besides driving to it is really really time consuming, because from Rome to Sicily it's a whole day journey, just for the drive and the ferry crossing.

So my suggestion is choose either of the following:
1. Sicily only
2. Campania (Naples Area) + Apulia
Two weeks are barely enough for either option. If you also want to spend time in Rome (if it's your first time, you need at least 3 days in Rome), then two weeks are really too short and you'll have to scale down your ambitions and select only parts of region 1 or region 2.

In Sicily: Siracusa and the Baroque towns in the interior (Ragusa, Noto, Modica); the Villa Romana del Casale near Piazza Armerina and the nearby Greek site of Morgantina; the Greek sites in the SW (Segesta, Agrigento, maybe others--I skipped this area); Palermo for the incredible churches, including Monreale; the historic hilltown of Erice near Trapani. Other picturesque spots: Cefalu on the northern coast (possible as a day-trip from Palermo) and the stunningly-situated Taormina on the east coast near Mt. Etna. Although I liked Catania's old town, it probably wouldn't make the cut if I had just 8 or 9 days in Sicily.

Try to scrounge a few more days. Sicily is worth 2 weeks easily.

Thanks for the feedback. The tickets to Rome are already purchased so that's done. Besides Naploli, Ercolano, Pompei and Positano where else should we go and do in that part of the country. We may rethink the 2 days in Rome bit but any guidance is appreciated.

With just 2 weeks, I'd save Sicily for another trip and focus on the southern mainland. Other than Pompeii and the Amalfi Coast area, you rarely see Americans in this part of Italy. You could slightly modify Rick's 2-week South Italy tour itinerary and do it in reverse. After staying a few nights in Eroclano and Positano, you could head east, to Basilicata as suggested by Roberto. I'd stay a few nights in Matera, then head into Puglia and stay a few nights in Lecce. Then head north, stopping in Alberabello to see the Trulli houses on the way to the Gargano Peninsula, staying a few nights in Vieste, before heading back to Rome for your last few nights.

Another vote for Matera, Puglia (I liked Lecce as a base) and the Gargano Peninsula.

Roma, the Amalfi Coast, Matera could easily fill two weeks, if you add a couple of nights in/near Alberobello and Vieste. Otherwise, you could go to the area near L'Aquila (highest point in the Appenine range, if you like hiking and Vieste.
Closer to Roma, the Castelli Romani would give you some off-the-beaten-track experiences.

Well have you ruled out Sicily? I think that would eat all of your time. So, what other places have appealed to you--surely you have done some reading and looked over maps, right?

You will not be missing tourists in Ercolano, Pompei, and Positano, so to really get off the beaten path, Calabria would be it. Puglia is firmly on the tourism radar, but it has nothing like the crowds of other parts of Italy and certainly would not in October. Basilicata is another great choice, and though there are certainly a lot of visitors to Matera, it is absolutely magical and there are many things to do in the vicinity.
The thing is, I could fill almost two weeks just in the Naples area--the islands, the lesser known towns of the AC--but a lot of that is weather dependent, so October could be iffy. I highly recommend including Paestum, just south of Salerno, and then just south of there is Cilento national park with some lovely towns, and then south of there you enter Basilicata and could stop at Maratea before heading inland. The only bad thing is having to choose among so many good options--I envy you!
ps If you are staying in Naples, I would pick up the car there instead of upon arrival in Rome (if you are flying from overseas). It will be nice to stay in Naples without having to worry about parking, and you certainly don't want to drive there. In October, crowds should have thinned enough that driving on the AC will be okay, but you will pay a premium for parking.

I will say that if you are foodies, Sicilian cuisine is totally different than the mainland and worth the trip. Certainly, it is somewhat pasta-based, but there is a sweet/sour, yin/yang quality to it that can't be found anywhere else in Italy. German, Greek & Arab influences abound. On our first night in Taormina, we feasted on an insalata with blood oranges, red onion, green olives and pine nuts, dressed with a viniagrette that was spectacular. This was followed by sweet & sour fresh tuna, with noodles that looked and tasted every bit like spaetzle, with red cabbage on the side. Delicious, washed down with a wonderful Nero D'Avola red from the slopes of Etna.

We flew from Rome to Catania & stayed in Taormina for 4 days--it was October as well--and the weather was temperate, in the 60's with occasional rain. Visited the medieval towns of Savoca, Forza D'Agro and Castelmola, the latter two were where the movie 'The Godfather' was filmed. And Taormina has the Teatro Greco, the Greek Theatre built in the 3rd century B.C. Acoustically perfect 2300 years later.

Again, if you have the chance, make it happen. It's unexpectedly great and you won't regret it.

It doesn't make sense to sleep 3 nights in Herculaneum unless you insist on having the car at that point. But why punish yourself visiting the attractions that are easily seen by public transportation with a car? Note that most visits to Sicily are done with an on-island car rental. Check rates, rules, insurance, ZTLs carefully.

OK, if you really want to go to Sicily after Naples check out the overnight ferry to Palermo. Leaves early evening, sleep in an inexpensive cabin, arrive Palermo early morning rested and ready to go.
Alternative...don't discount area west and south of Rome. The magnificent Villa D'Este gardens in Tivoli, the world heritage 12th century cathedral in Anagni, the historic and achingly charming hill towns such as Fumone, Piglio, and Subiaco in the Ernici Mtns, the awesome abbey of Monte Cassino, the moving US Cemetary at Anzio/Nettuno,etc... The tourists you will most likely encounter will be native Italians on day trips, maybe a few other Europeans and the local Ciociara cuisine and Cesanese wines will not disappoint. Also, if you get a chance try the porchetta in Arricia, ground zero for this iconic Italian specialty.

Thanks to all. I think we will take Rich's advice and keep it simple. I am sure that wherever we go we will not be disappointed. We don't mind a certain amount of "touristy" so the days in Ercolano will probably stay. Thanks to all again. It is obvious that more than one visit al Italia are required.