Biggest help in the beginning is to simply learn how to toggle between the different keystates as Drak stated previously.
Myself I have your shift key,ie thumb down button to redshift me,once here I use all my F' Buttons for extra controls,round red button for jump.
I dont use the scroll button for anything v.important,blink,or flametongue rockbiter,aspect of the pack ,you get the idea.
Oh and yes disable the diagonals on your thumpad .
I also have an MX-518,although here I use the top 3 buttons for my main shooting macros,(and Naysayer try binding the round redbutton for jump on your N52,its intuiative and much easier).