One of the major advantages is that ladder players have access to certain uniques (Reaper's Toll, Tomb Reaver), runewords (Faith, Fortitude) and cube recipes (upgrading exceptional uniques to elite) that non-ladder players do not.
I think ladder realm was created to introduce lots of new rune-words, Ladder only unique items, and as a way to purge duped items and hack programs.
Another difference is Ladder exists for a shorter period of time. It eventually get's turned into non-ladder with all the characters and their items converted to non-ladder wihout access to the newest ladder realm.
There certainly is less of the bad stuff going on on ladder...or so I hear, since I don't play non-ladder much these days.
to me, combining RUNES is the difference between ladder and non-ladder. You know, the chance to get BER and JAH in non-ladder is so low. (given that you don't buy those duped rune from ebay or trade duped runes with the others).
ladder give you a chance to cubing runes up to zod! I know it take hundreds and hundreds MAL or IST to make enigma BUT this is obviously better than to KILL AND HOPE ber and jah from monsters in non-ladder