Unfortunately no one site is always th best. You'll have to search multiple sites every time, each sit has its strong points and will find certain fairs others won't. As the above post mentions I always check ITASOFTWARE.COM. Although you can't book from their website you know you have not found the lowest fare if you cant match or beat ITA's lowest fare. Sites like Kayak are useful also, but no site I know of can compare all your options for you, so if you really want no be assured of getting the lowest fare you have to do a lot of searching every time.