Depends on what sound/tone I'm going for.
For funky rhythms and similar, I pick/strum pretty high up on the neck, actually...probably around 15th fret area.
For getting a little bit of Tele twang or really sharp, defined notes (arpeggiated chords, etc), I pick super close to the bridge.
For typical lead stuff, I pick pretty much right on the edge of the neck and neck pup.
For heavy riffing, pretty much right over the dead center of the bridge pup, allowing enough room for smooth palm muting.
For blues, etc, I tend to move all over the place, as movement of picking
jemsite.com/forums/tags.php?tag=location]location[/url] as well as shifting picking strength is pretty integral to coaxing expressive tones out of the strings.
Above all, I normally pick somewhere between but inclusive of the high and low E strings. I find that it helps a great deal.
