Originally Posted by LM225

It's a little more manual than what you're probably looking for, but you can put multiple originating airports into the "from" field in ITA matrix, separated by commas.

Example: iad, iah, sfo, dtw, JFK, atl

Then rinse and repeat until you find the lowest price.

I can usually get about 5 or 6 airports in there before it generates an error while searching.

Just remember to uncheck the box that says "allow airport changes."