Depends on the craft really. Stuff like weaving, alchemy, and cooking (at least in my experience) seem to be exactly the opposite; finished product with main hand, parts with secondary. As far as I can tell, it looks like the major difference comes when you HQ. One hand will give you the +1, +2, etc; while the other will give you increases in yield.
I actually wonder if there's any other difference than that. You'll see people say that some recipes respond better to certain tools, but unless someone has done some testing it could all just be a placebo effect.
Edited, Oct 17th 2010 5:26pm by Redyoshi