Getting a killer tone can be a bit of a challenge.It obviously starts with you having some idea of what you are hearing in your head or your own personal idea of a good/killer tone.A good starting point is trying to create the tone from one of your favorite guitarist,say Eric Clapton,Jeff Beck,Eddie Van Halen,Pat Metheny,John Schofield and others.Eric Clapton is known for his "woman" tone,it is a bluesy tone.
The fact is,it starts in the fingers.To me,the best tone is usually not using a pick,like Jeff Beck!The flesh of your fingers create a warmer,fatter tone.
When using a pick,the type material the pick is made of,has a huge variation on the tone,and the thickness of it.Along with how hard you hit the string,and the location where you are picking.Along with that,how hard or light you are fretting with your left hand.Of course another big factor,for electrics ,is how you have your amp set.Always start with your amps tone knobs set half-way,this is the standard setting from the factory for it's best tone,so start there!
But ideally,the fingers/hands are the starting point and big factor in your tone.Plucking the string lightly or "digging" into changes the tone.And as mentioned the pick and amp setting.All these factor into the "killer" tone!
eHow has some additional tips about tone also.I found some great info over that way....
More tips at eHow...
http://www.ehow.com/how_6310023_great-guitar-tone.htmland.. Jeff Beck...he is like NO OTHER
http://www.jeffbeck.com/index.php
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