(I know this probably sounds spammy but I promise it isn't)
If you are like my husband who just likes to book the first functional flight he sees this won't help. If you hate faffing around entering stupid stuff to get what you want it won't help.
However... if you are like me and want to book flights like "ok so I want to fly from here or here and go through here but not there and only at mid-day and I'd like a layover somewhere interesting and I'm not flying with (insert whomever you hate to travel with)" then you will love it too! I find so often I can't find exactly what I want when I travel and end up picking whatever is closest.
matrix.itasoftware.com
You can't book your flights with them, but it gives you a list of everything to take to the travel agent with or to call the airline direct.
I usually use kayak but was getting frustrated because I wanted a very long layover (3 days) in Paris on the way back and the only way I could do it on kayak was multi-trip and it cost a bunch. I got flights with KLM/Air France with a day in Amsterdam on the way and Paris on the way back for the same price as the trip was going to cost me without the detours! It took me forever to find the right combo but it worked a charm.
Hope it helps someone else!