My question is this, what direction should I lay out the long side of the
beds, E-W or N-S?

If there is any slope, crosswise to the slope.

Failing that, let's see, the main thing which springs to my mind is
putting the tall plants at the north side and the short ones south of
them, so they don't get shaded. That might argue for E-W beds. But
you have a lot of space.

40 feet by 100 feet strikes me as a big area to lay out in a strictly
rectangular way. But I guess I've always been the type to think in
terms of curved paths, aesthetically pleasing asymmetries, one part
raised a bit higher than the next, etc. I guess what I'm saying is
that if you've dealt with the obvious things, like slope if any and
what would shade what, I'm not thinking of a lot of considerations
other than aesthetics in terms of making the decision. There are some
rules to that (for example, rectangular arrangements and lined-up
sight lines for drama, or curves and little niches for intimacy and
variety), but it depends a lot on the site and how you see it looking.