First thing people are going to ask in order to answer this question is, "What do you use your PC for?"
If it's for gaming, you'll never use more than 8GB (in the foreseeable future), so if you're already set on going w/ 16GB then you definitely won't need to add memory before it's time to switch out your mobo for a new architecture anyway, so the 4x4GB would be the better option as it will get you better performance due to the quad-channel benefits.
However, if you use your PC for things such as video/photo editing, more memory is always better. In that case, I'd go with the 2x8GB to leave those extra slots open for a future upgrade.
In short, if you're definitely good with 16GB and don't think you'll ever need more until it's time for a whole new build, the 4x4GB is the way to go.