Experienced travellers to Greece often suggest that you get out to your first island as soon as you can immediately on arrival. Getting over jet lag on an island is way better than doing it in busy Athens. It is also important that you are in Athens at least the day before your return flight just in case something unexpected happens. We were booked on a flight from Naxos and there was a delay. There were several people madly trying to rebook their flight home because they were not going to get back to Athens in time.
While Santorini is amazing it is also expensive and really crowded when multiple cruise ships arrive. If you choose Santorini look for a hotel in Firostefani. It is just far enough from Fira that most of the crowds do not go that far. Its about a 15 minute walk into Fira.
If you choose Crete I would go to Chania. Its old town and harbour are a delight. You could also consider Rethymnon. Its harbour and old town is smaller than Chania but still a good choice. The bonus is there is a return ferry trip to Santorini a couple of times a week. You can still have the opportunity to see Santorini without having to pay for expensive accomodation.
