Now org-mode has improved and I disabled the slow parts,
and it opens very fast (<20 seconds). I still open large
files.
The problem may not only be in org but in emacs (e.g.
vc-mode can be slow), though from the instrumentation you
send, it doesn't seem to be the case because it doesn't
spend time opening the files.
org-agenda-prepare-buffers is the slow function, so
it's the one you should check. Try to use edebug in it
(C-u M-C-x) and run it slowly to see in which section it's
the slowest. Then optimize that part. You'll see many
optimization there (ignore properties, etc.). I had to
disable many slow things, like
<<<radios>>> (when you use a lot, e.g.
1000 per file, it's too slow and even crashes), I think
that these radio targets were the main reason of the
slowness.
Try creating a very large file and then check opening
it, to see if it's also slow.
Try things in a clean emacs (e.g. starting with: emacs
-Q), because you may have some other mode enabled that
wants to do lots of things when you open the files.
You can test many more things. But keep testing, because
it's possible to make it work faster.