I have been to Europe twice and am going to Italy over Thanksgiving. I have hit a couple of cities twice (Rome and Interlaken, Switzerland) but still enjoyed them a second time around. The other cities I have been to are London, Paris, Munich, Florence, Cinque Terre, Venice, and St. Andrews Scotland. There still are many other cities that I eventually want to travel to its just a matter of finding time and money.
As for advice pick a region and stick to that region. It really is impractical to start in London, head down to Spain, and then over to Italy. It is doable but you will spend a lot of time on the train or in airports traveling. For example its pretty easy to maneuver your self around a set of coutries like Germany, Austria, Switzerland, and Italy by using the euro rail. No rail trip is longer than 4-6 hours and you are able to hit a bunch of very cool cities.
I would bookend your trip with two different cities. Start at one place, do your traveling, and fly back home out of a different place. It is more difficult to travel throughout Europe and then have to short circuit your travels by making it back to your original city. As for a Mediterranean cruise I have always wanted to do that, just don't know about the state of Greece right now. I have also heard Athens has great land marks but itself is a dump.
I assume your an American. You will look American. No matter how much you try and fit in your still going to look American. I wouldn't worry about that too much. I have never had much of an issue being an American over seas. You just need to be a little more watchful of your personal belongings.
If you don't already have one, get an American Express card. They don't charge to convert currencies, most places accept it, and they offer travel insurance. Credit card is the easiest way to pay for many things as long as your card doesn't charge a currency conversion.
Finally enjoy yourself. Do find time to stay in a place for 2-3 nights and have a relaxing day or two. There are too many things to see in Europe and you will run yourself ragged trying to do so. Find some time just to relax, maybe a beach or lake town fits the bill. You will appreciate that.