I may be able to help, but, like others said, we need more details. Romelle's plan looks great... but also exhausting!
Greece is a safe, modern European country, so overall, you really don't need to worry about that (of course there are some areas in Athens that aren't fantastic at night, but nothing to worry about - I'm usually more concerned about my safety in Chicago or New Orleans).
Now - are you flexible within the month of September? It's a great time to visit Greece (nice and warm, but not the terrible heat you may endure in late July or August, and less tourists).
- How do you plan to get around? I hate to say it as I do encourage the use of public transportation, but to be comfortable, I would encourage you to rent a car, especially if you want to tour the Peloponnese. KTEL buses do exist, and are cheap, but may not necessarily make for a cozy ride. Of course, while you stay in Athens or Thessaloniki, a car would be more a problem than a solution.
-You won't find chain hotels everywhere in Greece, but wherever you don't, there are often comfortable and affordable properties around.
- When you say flying First isn't important, do you mean premium cabin isn't important or specifically First (as opposed to Business)?

With you Chase/Amex points you could look into transferring to Air France's Flying Blue (Look for availability before you transfer, transfers are usually instant). AF flies the A380 out of IAD. It's a comfortable ride in Economy (methinks), with a good amount of award seats, with decent food, and AF-AF connections at CDG are really easy nowadays. And it's only 50,000 miles r/t, with €45 fees to change/cancel. - again, just a suggestion.
Also, since you have the Sapphire reserve, keep an eye out for sales to Europe: they happen pretty frequently these days - but it's maybe a bit early for September. You could end up spending a lot less booking directly with Chase UR travel if the ticket cost is around $500 - (you'd only need to spend 34,000 UR points per ticket). Again, just a suggestion!


For culture, I'd say Athens, Delphi, Olympia, Epidaurus, Mycenae are a must-see, and they are within a rather small radius, but again, Greek roads aren't wonderful.

For relaxing - you could look at Kalamata, or Tolo, or Euboea, or even smaller islands (fly Aegean within Greece, they're a nice airline, and cheap, so don't bother with miles for domestic flights).