If you are using a Froyo ROM and have moved apps to the SD, I wouldn't mess with .android_secure.
Other than that, there are ZERO folders that are REQUIRED.
Having said that, different apps store all sorts of things in all sorts of places on the SD card, so if you were to erase your entire SD card, you might get different behaviors in a few different apps. For example - you might have ringtones assigned to contacts, and those ringtones could be on your SD card.
But, it is highly unlikely that your phone would be rendered unbootable by erasing the whole SD card.
There are some places that you definitely would want to preserve, even though they are not REQUIRED:
/sdcard/nandroid/HT9* (your nandroid backups from Amon_RA, if any)
/sdcard/clockwork/* (clockworkmod and nandroid backups - if you use Rom Manager)
/sdcard/dcim (your camera pictures)
etc
