First I tune the low needle since it has more of an effect on the high end mixture than the reverse situation. Once the low needle is perfect I do a check on the high end. It it drops RPM's at WOT after a few seconds it's to lean. Richen it a little at a time until it holds a constant WOT RPM for at least 5 seconds. If the WOT RPM's rise slowly it's too rich. Lean it a little at a time. A lot of times after you tune the low end the high kind of rides with it and really doesn't need much adjusting if at all. Always check to be sure though.

Adjusting with the engine running gives you better and faster feedback but has its risks. I've done both, it depends where the needles are. For a rear induction it's possible. For a side induction with the needles pointing forward, forget about it.