For instance, TDT implies that one should one-box even in a version of Newcomb's in which one can SEE the content of the boxes. But would a human being really leave the other box behind, if the contents of the boxes were things they REALLY valued (like the lives of close friends), and they could actually see their contents?

Probably not, and thus s/he would probably never see the second box as anything but empty. His/her loss.

I think that would be hard for a human to do, even if ex ante they might wish to reprogram themselves to do so.

I think it's hard because most human's don't live their lives according to principles. They care more about the lives of close friends than they care about their principles.

In the end reprograming yourself in that way is about being a good stoic.