If I'm not mistaken, 16-bit is "only" the number of colors that can be saved in the image format you are using.
I'd say then it depends on your image editor.
Also I suggest you this blog article
about C2's image compression which could help you deciding if 16-bit is the way to go for your game.
I'm not a confirmed graphical artist though, so maybe there is some shade I'm missing in your question.Kyatric2011-12-25 11:00:44