Would it make a huge difference substituting margarine for unsalted butter when making biscotti?
You could try a taste test if this is an important thing for you in the long-term. I don't think the margarine will deliver the best flavor, honestly. Cookies really are about that rich butter flavor. Biscotti do have less butter than most other cookies, but I still think you'll find the flavor is better with butter!
I make biscotti frequently using a recipe with no butter at all, which is very common and even (I think) traditional. Eggs are the only fat in the recipe. They taste great this way. However, if you want to use a recipe that calls for butter, personally I would use butter. Margarine will work but you won't get the same great flavor butter has.
P.S. Next time try the Home Cooking board -- lots of skilled bakers there.