How much time do I need between flight from Santorini-Athens and Athens- US?

While you will have lots of time to make that 4:45 flight most of us here would suggest you fly back to Athens the day before your return flight
Last year our flight from Naxos to Athens was delayed for 4 hours. (Stuff can happen to all airlines around the world ) We were flying the day before our return flight. No problem. There were French, American, Brits and South Africans who planned to catch connecting flights home that day. None of them made it You have a 99.9 percent chance of making your connection. Unfortunately if you are in that .1 percent its an expensive mistake.

How firm is your plan? Can you re arrange and do you have the option of flying out to your first island the day you arrive. Then you can head back to Athens early and so your visiting at the end of the trip.

Stanbr has it right. By all means save your time on the mainand for the end of your trip or take the chance of missing your flight home. Another factor is the poor functionality of the Santorini Airport at the moment. Flights are often delayed because the airport is in such organizational disarray. Although you seemingly have plenty of time to make your 4:45 flight things could go wrong with no warning.

As always, if you're booking the first flight on a separate ticket, you have no recourse but to buy an expensive one-way, trans-Atlantic ticket if you miss the second scheduled flight.

I can only relate that when we were in Greece in September one year, winds forced ferries to shut down a couple times and disrupted air travel. Much like Schools in my neck of the woods cancel if snow conditions exist, Greek travel stops under certain conditions or is delayed. Will you be OK? if everything goes right, but it is a gamble. I would opt for flying back to Athens at least the day before, leaving yourself some room for the unexpected.

Ok thanks all-- you have convinced me to do the prudent thing. Booked my flight to go straight to Islands first, and returning early the day before my flight so will spend last day in Athens and not risk missing flight home!