As discussed here:
http://www.byond.com/developer/forum/?id=751409
Having organized directories can inflict a rather hefty speed penalty unless you go through the trouble of manually denoting file locations.

Would it be possible for DM to somehow store file locations the first time a game is compiled, then on all subsequent compiles it simply assumes they are in that location, and doesn't bother searching through folders for them unless the file no longer exists at that location?

And as discussed here:
http://www.byond.com/members/ DreamMakers?command=view_tracker_issue&tracker_issue=1525
It seems like map compilation (and/or map saving) could be improved.

Though this isn't a problem on smaller projects, which compile more or less instantly, larger projects can take nearly a minute (or more in some cases), and DM becomes unresponsive during that time.