I'm checking out what could be the best way to get to Turkey from North America (JFK, LAX, MEX, ATL are all possible departing airports depending on airfare). Crossing the Atlantic is actually no biggie, my primary question is if I should look for a direct flight to Istanbul, which could prove to be more expensive (and I doubt it would be a non-stop flight), or if I should aim for London/Frankfurt then RyanAir somewhere "close" like Budapest then move on via train to Turkey, or aim for Rome -> Brindisi -> Greece -> Istanbul.
Overland travel in Europe will not likely make your journey cheaper, even though you can occasionally get a cheap long distance bus trip through one of the Eurolines partners.
On the other hand, overland travel in Europe can significantly enrich your experience, so the additional cost might be worth it anyway. Then again, Istanbul being on the edge of Europe, it will be difficult to get there, overland, from nearly anywhere in Europe, at reasonable cost.
So, that probably means you're left with flying.
You should try the usual suspects, Hipmunk, Momondo and the new kid on the block with interesting results for Europe, Adioso. And, as Mark points out, you can try Flightfox, particularly if your departure and arrival airports are so flexible.
Then again, a quick search shows that Turkish Airlines flies from New York to Istanbul and back for the low, low price of 656 USD. In January. That's ridiculously cheap.
A colleague I work with recently spent a few weeks in Europe (from Vancouver). We hunted for flights beforehand, and one of the key 'tricks' to saving money was to simply look for any flight into anywhere in Europe. We looked at the major hubs - LON, FCO, AMS and more. From there, you can look at RyanAir and Easyjet, as well as bus/train options from there to Istanbul.
One more option to try is Flightfox. They crowdsource 'experts' who search for flights for you. So you can specify your criteria, no matter how bizarre, and have experts search for the best flights for you. It's not free, but if you look at my profile on here, there's a referral link for 25% off. (Disclosure, I'm one of their 'experts' who hunts for flights). Say that you're prepared to fly into anywhere in Europe before flying to Istanbul, for example, and you may be able to save quite a lot!
(with my colleague, in the end they flew into AMS, and then had a one-way ticket to FCO. They then travelled around by train, returning to Amsterdam and flying out once more)