Ideally every thing should be grounded. I'd run the negative cable to a starter or bellhousing bolt. Then I'd add a strap from engine to frame, another from cab to frame and another from bed to frame.
As far as running the harness, take it a piece at a time. I used a Hot Rod Wires harness on my '56. I mounted the fuse box first then ran each system one at a time from there. I left the rest of the wires hanging out the door while I was working. I know it looks scary when you look at that big old bundle of wires, but as long as you take it a piece at a time it's manageable.
Good luck.
