Do saddle ergonomics matter if you've got padded shorts?
The short (pun intended) answer is "yes." Or at the very least, "probably yes." One of the big things that makes saddles uncomfortable is pressure on the soft tissues between your "sit bones" (the ischial tuberosities). It may seem counterintuitive, but padded saddles can make this worse. The problem is that the padding allows your sit bones to sink into the saddle increasing the pressure on your soft tissues. Padded shorts won't do much, if anything, to prevent this and may actually make it worse.

What you want is a saddle that supports you sit bones with enough conformance to avoid pressure points around the bones, but without so much give that you end up carrying your weight all across your "bottom." On a saddle that basically works, but where you find yourself getting sore around your sit bones, padded shorts may help. But a good saddle is a lot like a good hard chair – you can sit on it for hours. You'll get tired of sitting before you it becomes uncomfortable from the pressure.

In my experience the benefit of the chamois is in minimizing chafing, not in providing padding.