Check to see if you have backups running WHM and if they are see what you have them setup to backup. Also if you don't have your accounts default address to :fail: then run something like this
du -h /home/*/mail/inbox | grep M | sort -n | tail -10
and
du -h /home/*/mail/inbox | grep G | sort -n | tail -10
I caught a customer of ours once with a 10GB inbox file.
try doing this from /home/
du -h --max-depth=1
It'll help determine which user has been using the most diskspace.