How to isolate the most disk-active process(es) in OS X?
After fiddling with making my own solution via fs_usage manipulation, I discovered the DTrace iotop script (man iotop).  This really seems to do the trick with regards to giving samples of filesystem activity at nice updated intervals and quickly allows one to isolate possibly misbehaving processes.

*NOTE: you must run it with sudo or as root user.

For example:

sudo iotop -C 5   # Simply gives an update every 5 seconds in default output format without clearing screen.
sudo iotop -CP 2  # Gives 2 second interval updates w/o clearing screen and I/O time based output.


Options:

iotop [-C] [-D|-o|-P] [-j|-Z] [-d device] [-f filename] [-m mount_point] [-t top] [interval [count]]

   -C     don't clear the screen
   -D     print delta times - elapsed, us
   -j     print project ID
   -o     print disk delta times, us
   -P     print %I/O (disk delta times)
   -Z     print zone ID
   -d device
          instance name to snoop (eg, dad0)
   -f filename
          full pathname of file to snoop
   -m mount_point
          mountpoint for filesystem to snoop
   -t top print top number only