So I can select an area of a column "=SUM(B2:B50)" and have it add and produce a total in say B51. That's fine but fairly simplistic and I need more. Completely new to spreadsheets and how to do this stuff.
You'll want to read a book, go on a course, get local help, join a club, or whatever. You cannot really learn by individual e-mail message.
1. Can I add ALL of Column B, Minus B1 and have the total of the column display in B1?
You don't mean - do you? - that you want the existing value in B1 subtracted from the sum of the rest and the result put back into B1? That would be a circular (or "recursive") requirement and the result would be undefined. If you just want the sum of the cells from B2 downward placed in B1, just put
=SUM(B2:B999)
in B1. Choose a finishing row that will be beyond any values you will insert. If necessary, find the last possible row number and use that.
2. Column B is a Cost/Each, C is Quantity, D is Shipping & E is Total Cost. Is there a way to multiply B & C then add D and display in E for each row?
In E2, enter:
=B2*C2+D2
and then fill this down column E as necessary. For an understanding of "fill", see my first sentence above.
Yes, I understand C would have to be at least 1 or greater and not empty. 
Not particularly. Empty cells are evaluated as zero in calculations. But you will have the problem that your customer who orders none of something will still be charged for shipping his non-existent package!
I trust this helps.
Brian Barker