Istanbul - Athens - ???

You'll love Istanbul. It's amazing. Be sure to visit the Grand Bazaar as well as the Blue Mosque, Agia Sophia and Topkapi Palace. It makes the best sense to take the train from Athens to Thessaloniki, have a look around before continuing to Istanbul, then fly back to Athens for your flight home.

Two places to consider for an additional Greece visit:

Go south and a bit west of Athens, to Nafplio, on the Peloponnese peninsula. You’ll cross the Corinth canal. If you’re up for driving a rental car to get there, you’ll be able to also see ancient Greek sights like Nemea, Mycenae, and/or Epidavrus. Nafplio has a great outdoor market, and other fantastic food possibilities.

Or head west of Athens, staying on the mainland, to Delphi or Galaxidi. We spent one night in Delphi, just down the road from its ancient site, then switched to a tremendous mother-and-daughter-run B&B in Galaxidi. The two cities are just a few miles from each other, so you could easily visit one while staying in the other. Delphi is small, but was too noisy late at night for us to be able to sleep. Galaxidi is right on the coast, and the seafood couldn’t have been better. Either will take less than a full day to reach.

I vote for Nafplio and take day trips from there.

I agree with trying Thessaloniki. Two Greek expats here insist it's better than Athens. I have no knowledge - but my surface research found it interesting to add to our next visit. It is a bit off the normal US traveler's path so might be fun to explore

Suggestion might be - multi city flights - into Istanbul - to Thess... - to Athens - flt home. or in reverse. We have flown Turkish Air and been very happy with the flights and service. The new airport is plush, huge and pretty easy to navigate.

I would also suggest Thessaloniki, I've never been there myself but I've heard a lot of good things about it. And for a bit nature or smaller towns, the nearby Halkidiki peninsula can be worth exploring.

Rather than visit a 3rd city have you considered visiting one of the islands? We spent 3 nights on Santorini a few years ago and really enjoyed it.

Wife and I did the trip in reverse - Istanbul first, then to Athens; and continued to Santorini and Mykonos.
In planning for Istanbul make sure your visit does not fall within Ramadan as the bazaar will be closed.
If you take on an island or two fly; the ferry ride while somewhat scenic is long and crowded.

The sunset view in Santorini is unparalleled. Find accommodations that face the caldera; best place to enjoy the view while having breakfast.

Visiting Santorini is another good idea although Nafplio would be easier.

You are aware that there is no train service between Istanbul and Athensl? There are flights, but the only two ground options are Istanbul-Thessaloniki by bus (10 hours overnight) and on to Athens by bus or train; or Istanbul-Sofia-Thessaloniki-Athens by train (much longer). Best to fly.

I was not aware of that change. If memory serves, there used to be train service from Athens to Thessaloniki to Alexandroupoli, then a bus from Alexandroupoli to the Turkish border followed by another bus the rest of the way to Istanbul.