2 Week Greece Itinerary

Driving a car right after getting off an overnight flight that crosses time zones is really not a good idea.

DRIVING ON ARRIVAL DAY ==
Depends on how old the OP is, and what level of airline ticket they're plunking $$ for.... If they're no more than middle-aged, and can catch 4 hrs of sleep on the plane ... and quaff 2 strong expressos when they land, they can make it to Delphi OK, little traffic on that road in Midmay... check into hotel, catch 2 hrs late-day nap, then go see the Museum from 5-7 (it's EMPTY at that time!) Early bedtime, enter ruins site at 8 AM, again, almost no one there ... you'll be way up top by time the bus-tour throngs pour in.

ARGOLID AREA -- good plan . You can avoid backtracking by saving Epidaurus for AM on Day 5, don't have to stay long, the theatre is the main thing, then drive up the Coastal road to Isthmus, spend 15 minutes by Old Bridge to check out Canal then hit the Big Highway to Athens area.

CRETE
YEs you can pick up car in Chania, drop in Heraklion NO problem no fee. HoweverI would spend at least !! one niht in Chania!! Loveliest old-Town in Crete!! (2nd loveliest in Greece, bested only by Nafplio). And as long as u have a car, why not go south and enjoy PHaistos enroute & catch a glimpse of Lybian sea? Here's my suggestion based on 3-4 great trips; use this map to track: http://www.explorecrete.com/crete-maps/images/Crete-eot.png (click & it gets huuuge).
Day 6: spend day in Chania, check out museum (maybe eve a late day dip in town beach) harbor sunset, great meal, stay in little pension on Theotokopoulu Street (casa di pietra, Pension Nora many others). No need for car this day.
Day 7 - Car delivered near hotel -- drive modern hiway (Big GREEN road) on Map to Rethymnon area (or do cute inland Old Road & see lots of sheep/goats & little villages), At Rethymnon, Turn south on (Red Road on map) thru SPILI (village with AMAZING ancient lionhead fountains!), continue to MATALA - I recommend Villa DImitra, back from beach, view of mountains. Climb caves above beach, have a dip, enjoy sunset, check out KOMO archeology dig nearby.
Day 8 - In AM, go to Phaistos & Then Ag Triada then Drive thru Mires, on same Red Road, N.E. to Heraklion Area, to hotel.
Day 9 - Knossos & the museum -- some like to do the Museum first others the ruins.. If you do ruins first, get there by 8 AM to beat the cruise-ship crowds. Otherwise, get to site after 2 pm, when cruise & bus crowds start leaving. Fortress on causeway is a fun walk before dinner ... there are fab "meze" places right on traffic circle at foot of causeway.
Day 10 - 14 as stated.

Well my two cents would be to catch a flight to Crete a few hours after landing in Athens. We flew to santorini after landing and I think going to an island and wandering around is far superior to trying to see a museum that evening and being at a historic site at 8 am the next morning. But of course this is only sensible if you follow Janet’s advice of spending at least one night in Chania. This also avoids over night ferry ride. Now I have not done this but in my twenties used to take overnight train rides and never got much sleep.

You then can take ferry to santorini and fly back as you proposed and then rent a car to drive to Delphi.

I think this sequence would be more enjoyable.

Hey, thanks for all the advice.

We generally don't have too much of a problem with jetlag or timezone differences, but it will be a long day, we might have to rearrange our first day.

As for Crete, we'll definitely make time for a night in Chania.

As long as you are flying direct to Athens on AC Rouge or Air transat you will be arriving around 9:30 in the morning. As Jan says force down lots of coffee and you should be able to drive. If you are taking a flight to Europe and connecting into Athens that will get you in late afternoon. I would not recommend driving after that flight.

Your plan can work as it is. If I were doing it though I would immediately fly to Chania and spend a night or two there to comfortably get over jet lag. In two days you will barley be able to find your way around Chania old town back alleys.
Chania http://www.flickr.com/photos/stanbr54/sets/72157632117917828/

Then rent the car and drive to Heraklion.
Heraklion https://www.flickr.com/photos/stanbr54/sets/72157655935354556

On your day trip to Phastos and Agia Triada find Gortyz or Gortyn. It was the Roman capital of Crete and the city is still lying there in olive groves. It is an unofficial site and preliminary excavations have been done but when you get there you will feel like you discovered a lost city. It was the highlight of our trip.
Gortyz https://www.flickr.com/photos/stanbr54/albums/72157666456665788
Crete Archeological sites https://www.flickr.com/photos/stanbr54/sets/72157645085297380/

While on the mainland on the drive back from Delphi you essentially have to drive by the ancient site at Nemia. This is a good time to stop and visit Nemia so you don't have to backtrack on you Mycenae/Nemia day.
Nafplio and Peloponnese http://www.flickr.com/photos/stanbr54/sets/72157632094108982/