Picking up, and returning a car in a big city is always easier at an airport or other location outside of the congested city center. That often comes at a higher price, due to airport pickup surcharges, or extra driving distance from where you might be coming or going, but the convenience usually makes it worth it.
Although Greece has all the big rental companies companies like Hertz, we rented from Pop’s, a Greek company with several locations. We rented at a small port town on the Peloponnese peninsula, south of Piraeus, then turned it in in Athens (airport), so they allow pick up and drop off at different places.
We get the smallest (so, also cheapest) size car that will fit the number of people, and luggage. Better gas mileage that way, as well. We both drive manual transmission cars at home, so we can get them on trips, although many on this Forum are adamant about only renting an Automatic.