Actually I don't know any more than you do. SUroot used it for a while, and decided that he didn't think it was a good idea. I didn't even have a high-speed card, so decided it definitely wasn't for me. For space I preferred to use a small ROM, custom HBOOT (to get more real internal space) and use a2sd in addition (moving apps with large library components and no widgets to sd the traditional way, as that does save extra space). I'd take AOSP ROMs which were already small and strip out stuff I didn't want, so I was running different AOSP ROMs in system partitions between 75-90 MB. Of course if you really wanted to maximise you could take dGB and add an a2sd script, but since SUroot built that one precisely so as not to need a2sd I always felt that would be disrespectful (though with a 60MB or 65MB hboot and judicious use of move to SD you could fit a surprising amount in with that ROM).
One thing I would check: some a2sd scripts move the dalvik cache, and some don't. Moving dalvik does slow the phone down, but it's a small effect, and unless you are already running a very fast ROM you won't notice it. It does however make a huge difference to space, so if you aren't moving the dalvik cache and are short of space I'd try that first. Don't worry about speed, because data2sd will be slower. AOSP ROMs that don't move dalvik usually have an option to do so (sometimes flashing a different a2sd script).
But yeah, there are limits to what you can do this way, and if you exceed them all I can suggest is get a fast card, a largish partition, and try a few and see what data2sd works. Nandroid first, of course, in case it doesn't work out.
I will confess that I'm not at all unhappy not to have to worry about this stuff any more!