Istanbul to Athens

If expedia is any gauge, a rental car from Istanbul to Athens is not possible

Agree with the above. I think it's very unlikely you will be able to do what you're describing (because of rental car restrictions, or astronomical fees).

If you really want to drive, consider booking two cars, one for each country. Drop off you Turkey car before you cross the border into Greece, then take public transit of some kind across to the next town, pick up your Greece car there, and drive onward. The trick will be to find a pair of towns close to the border, each with a car rental agency. I've done this country/car switcheroo several times (although not at the Turkey/Greece border) and it's possible but requires a bit of research and planning, and it always seems to take a little longer than expected. It can be a bit of a hassle (or an adventure, depending on how you look at it) but can give you great freedom, and/or save you a ton of money.

I'd fly from Istanbul to Izmir, and visit the spectacular Ephesus.

Then ferry from nearby Kusadasi to the Greek island of Samos. Then either fly back to Athens, rent a car and visit the Peloponnese. Or island hop back to Athens. Go to http://www.gtp.gr/ for schedules.

Samos has 3 ports you can catch ferries from: Vathy (main port) and Karlovasi, from which you can ferry to Fourni>Ikaria>Syros and then on to the Cyclades islands or back to Pireaus (Athens).

But if it were my trip, I'd use Samos (Pythagorion) port and head south to the Dodecanese islands. You can visit any or all of Patmos > Lipsi > Leros > Kalimnos > Kos > Nisyros > Tilos > Symi > Rhodes. You can fly back to Athens from Leros or Kos or Rhodes. My husband and I did a similar trip and visited all but Kos and Kalimnos. Each has its own charm. We especially loved Nisyros. It's a tiny island with an active (but not erupting) volcano that you can hike into. An experience of a lifetime. You can get there on day trips from Kos or (my recommendation) spend a night or two on Nisyros. At that time of year, you don't need advance reservations on these islands except maybe for Rhodes? Just call ahead the night before you're heading out to find accommodations on your next island.

If this is your first trip to Greece, plan to arrive in Athens three days before your flight home, to give you time to see the city.

This is going to be more difficult than I expected. First off, car rental from Turkey through Greece isn’t going to happen. Even tried a rental from Alexandhroupoli, Greece west to Athens. Not happening.
Charlene, thanks for the ferry link. That will be very helpful.

Prefer to spend at least 3 nights in a place, more for big city, so 3 weeks doesn’t go very far. Looked at some of the islands on google, Samos, Hios, Kos, Náxos, Santorini. From afar and without a deep dive into what each has to offer I feel bewildered.

One idea is going from Istanbul south to a ferry port along the Turkish coast and grab a ferry ride out to the Aegean but the time spent on a boat looking at nothing but the sea, going from port to port, for hours on end is not appealing. I served in the navy at sea for a few years. I’d rather look at the hills and trees, etc.

What would it be like to drive along the coast, either side east or west coast of Greece south to Athens?
Lastly, I can only absorb so much of museums and architectural artifacts. I will never see everything but I will appreciate the things that I do see.

One way or another, I want to fly into either Istanbul or Athens and leave from the other.
There is a lot of “but”s in this post -but- this is how I process.
Thank you all for help and patience. It is appreciated.

You have so many options already but let me clarify one and add another.

By Greek island hopping, I mean spend 3 days on Samos; hop a ferry to Patmos, stay 3 days there; and so on til you run out of time, then fly back to Athens for 3 or 4 nights. Each island has its own highlights; which islands you choose depends on your interests. It just takes some time with a guidebook or Matt Barrett's website to acquaint yourself with them.

However, I get the feeling you'd rather drive than explore islands. So another option would be to visit more of Turkey before heading for Greece. In this case, fly (or drive, but it's at least 9 hours) from Istanbul to the Cappadocia region. Stay for 3 or 4 nights, explore the region and do a hot air balloon ride. We enjoyed staying in Goreme, in the Kelebek Hotel.

Then drive toward the coastline, perhaps to Antalya or to my favorite, tiny Patara (stay at Akay Pension). Travel north up the coast. You can visit places like the Saklikent gorge; Dalyan , where they have a sea turtle hospital and Lycian tombs carved into the cliffs above the river (stay at the Kilim Hotel); and Bodrum, a popular seaside getaway. Proceed north to the previously-mentioned spectacular Ephesus, then catch the ferry to Samos. Spend a few days there, then fly to Athens. If you have a few days remaining, visit Delphi and/or Meteora and/or Napflio in Greece.

Hope this helps!

This is all great stuff. What I get is that I need to do a lot more study. Good to hear that lodging on the islands may not be a problem. That gives me a lot more flexibility. Never thought about using a overnight ferry ride to take care of those big chunks of space.

Thanks for the ferry link. That will be key for sea travel. At this point I’m going to make my airline connections, read, search the nets ( Google is so good for getting a feel for a town or place: pictures fill in the narrative)

My travel partner is/was very reluctant to fly, let alone tour Turkey. In fact, in the past, we have forgone a cheaper Turkish Air flight in favor of a more expensive and/or longer airline connection because of her fear that bad things are happening there?. I finally have convinced her, or wore her out, that we will at least visit Istanbul. Having her read these posts and other info on RS forums is helping. I know once there and among the folks, she’ll be fine.
That said, I really want to absorb as much of that area as we can. As always, more is not necessarily better.