After a long time working in the background, I have started the process of making USE_DESTDIR=yes the default behavior.
The first step was making developers use it by default.
This has a number of implications:

After a small round of changes with the help of tnn, "make replace" now fully works with USE_DESTDIR as well.
Before, it couldn't replace identical versions. The new pkg_add -U option explicitly handles that case.

What next? There are still slightly over 600 packages that don't support USE_DESTDIR.
I hope to further reduce this to 400 or so, at which point the current warning will turn into an error.
I plan to make USE_DESTDIR the default soon for all useres, "make replace" was the last major blocker.
Hopefully, in the second half of 2010 it will be required and support for USE_DESTDIR=no can be removed.