The Lowest Fare? Ask the Crowd
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The best offer I get that actually read that instruction knocked $3,000 off the $5,000 that Delta.com quoted me. I went with Delta. I have the utmost respect for the amount of searching which went into it, but the instructions I got back were 6 steps long, with each step sounding like "Book a one-way flight from X to Y using this web interface", and I was terrified of getting halfway through and then being stranded in Des Moines not able to book the rest of the flights at anything near the quote.
I'm so there if they can handle the bookings themselves, such that I'm not the one bearing the risk-of-failure-to-book.
http://www.startupsmart.com.au/success-stories/flightfox-acc...
http://www.skyscanner.net/flights/lond/berl/1302/1302
There are definitely challenges in gathering & displaying a combination of budget and 'traditional' carrier fares, but to say that either set isn't available via flight search isn't accurate
You don't really have a control group to know that skyscanner consistently provides the best results. It's possible that you were happy with your skyscanner experience and believe that you got the best deal, while there was an alternative that would have been much better for you. Flightfox is a relatively cheap insurance policy against that.
I tried it out and the winner quoted me an incorrect itinerary cost -- didn't notice that the airline's quoted price did not include airline fees and taxes (which are in the hundreds of $$ for international flights). In the end, the true winner beat skyscanner by less than the cost of the contest.
Honestly, I find skyscanner amazing; it is the only system I know that finds airline consolidators (well flightfox does of course too) - and has a very easy to use tweaking interface.
The only thing I'm worried about now is somehow getting my luggage wired through all legs of my trip rather than my having to go through immigration at each stop and pick it up, only to go back through again and drop it off :P