Well I can attest to the fact it is a very long flight sequence to get to Athens from the west coast. It took us a full 24 hours of travel in June this year.
Experienced travellers to Greece often suggest you get out to your first island on your day of arrival in Athens. It is way better to begin your trip on your first island than spending that night in Athens. If you arrive Santorini in the evening it has the effect of giving you several hours the next morning to start your Santorini experience. If you waited overnight in Athens you will lose a substantial chunk of the next morning just getting to Santorini and then transferring to your hotel.
The two airlines I would trust are Aegean/Olympic or Sky Express. They are both Greek airlines and have good reputations.
You need 2 hours to make a connection. Most of the time we have done it in an hour and a half but 2 hours is better. Don't even think about trying to make the 50 minute connection.
Here is what you can expect in Athens airport.
I am assuming that your Santorini flight is a second ticket. So you will have to gather your bags then proceed to passport control. If you have booked your transatlantic flight on a Star Alliance airline on a single ticket on Aegean your luggage will be checked through to Santorini.
If you fly Sky express you will need to pick up your bags and then check them at the Sky Express counter. If possible try to just bring carry on luggage.
So pick up your bags go directly to Passport control. The longest we have waited there was 20 minutes. Most of the time it is a quick process. When your passport is stamped proceed to the exit door. There is no further checks just walk through the door marked Nothing to Declare. You are now on arrivals level.
Go up one floor (stairs, Elevator or Escalator) You are now on departures level. Drop off your bags at the Appropriate airline counter and look for Security. I forgot to mention both Sky express and Aegean allow you to print your boarding pass 48 hours before your flight. You do that and you will have the boarding pass before your first flight takes off in the US.
As I recall there was a place where you can use a machine to print your luggage tags and there was a drop off machine nearby so you may not have to go to the airline counter to drop off your bags.
On our return trip in June the airport was very busy and crowded. There were hundreds of people in the security line. Athens airport is also very efficient. They have people stationed in the area who direct you to the next available security desk. It took us 19 minutes to get through security. Considering the size of the crowd that was remarkable.
Now find you departure lounge. You will probably have sufficient time to have your first Mythos while you wait for the connecting flight.