Cornwall and Devon

Truro would probably make a better base as it is more central than Penzance. Where you you flying from? Exeter does not have trans-Atlantic flights. Newquay is the main airport serving Cornwall but has relatively few flights. October can be stormy as you are approaching winter. (The Caribbean hurricanes often end up crossing the Atlantic losing power on the way).
https://www.visitcornwall.com

I agree Truro is a better base. Penzance is a dreary town at the far end of Cornwall, Truro is more central.
Don't miss St Ives.

Where are you travelling from? Exeter has few international flights, Newquay has fewer. If you are travelling from somewhere in the UK, train is also possibly, but it takes a long time to get to Cornwall. A car is needed to tour Cornwall.

There are several attractive small towns in Cornwall which could be the base for a holiday. I assume you will hire a car. Think about Falmouth (www.falmouth.co.uk) or St Ives (www.stives-cornwall.co.uk). I have been to both and can recommend them. Falmouth is a deep-water harbour with several interesting creeks (ie river valleys flooded by the sea), while St Ives has three beaches, art museums and a thriving art scene. Both would be more interesting than Truro, which is inland.

Mevagissey / Fowey / Polperro
... the places I like to recommend.
(We stayed near Polperro for a week)
Distances are greater than you think, and driving slower than you expect

You can get some fast-travel timing ideas from Rick's South England tour itinerary, but allow more time, if you have it. That tour didn't have time (or maybe a small enough vehicle) for some spots of possible interest like Mousehole or the Minack Theatre. The Geevor Tin Mine is worth a good few hours. Rick's most detailed coverage is in the England book (not the Great Britain book).

I went to Cornwall this summer and had Penzance as a base. If I were to do the trip over again, I would have stayed someplace further north. I loved Falmouth. Wonderful seaside town. Close to Port Isaac is Tintagel. Tintagel was the highlight of the trip for me. You can do both Port Isaac and Tintagel in one day. Make sure you visit Tintagel on a day that has no rain. You will be climbing many rocks that become very slippery. I was going to suggest a Western Discoveries tour but I just looked at their website and they will not be doing any tours in 2017 which is a shame. I don't have any recommendations, but I do suggest taking a tour of the peninsula. There is so much history in the area. And don't forget to eat a Cornish Pastie!

Thanks to all for the assistance. We are coming from US through Dublin and then a flight to Exeter where we will hire the car. Return the car at Exeter and train to London

This would give you some flexibility and get you to all corners of Cornwall.

Plymouth (2 nights)
St Ives (2 nights)
Padstow (2 nights)
Exeter (1 night)

We've just returned from Cornwall, which I love. We stayed in Port Isaac which is close to Padstow, Tintagel, Boscastle, etc. I prefer the wild, dramatic Atlantic side of Cornwall but others prefer the softer eastern side. I would definitely recommend staying in a seaside village or town and not an inland city. Driving takes much more time than you'd expect, as the others have said. Email if you have questions. Julia

I'm trying to plan my trip from the US as well for Cornwall for mid-September. I'm interested as well in how many days I should plan to devote to that area. My husband and I (active seniors) will be renting a car in Bath and driving down. Should I stay in one central location as a base or would you suggest I stay at a different area for say 1-2 nights at a time to move around. It's my first time driving and I'm trying to figure out distances and all of your comments are so very helpful! Also, any recommendations on moderate accommodations would be so welcome.

Ditto Dave in Brisbane. Except I like Mevagissey. Small, walkable towns. St. Ives too full with tourists..er. and Falmouth is too big. IMHO.

Terry, As another active senior, I'd decide what is most important for me to see and stay within as easy a distance from them as possible. Moving around is such a bore. Staying put also means you can have your own "local" for a few days. One year we stayed in Mevagissey and Tintagle was not to far for us to drive. Another time we stayed near Red Ruth. The roads can be narrow, but the driving is fun and sometimes you just have to get up a little earlier.

Boscastle I love. We had 4 nights there and covered Port Isaac, Penzance, Padstow, Eden Project, Lost Gardens of Helligan and lots of places in between. We prefer small local villages to large towns.