it depends also on where you are picking, in relation to where you are fretting. If you are hitting an open note, and you are picking at the bridge, then it is tigher, and leaves less restriction or "pull" when picking. Thats why you can tbend the string easy on the first or second fret - its too close to have any give to it.
But... if you were to pick an open note at the 12 fret, then it has more give to it, and will be more difficult to speed pick on, since it will most likely pull on your pick more, making it catch on the string. When starting tremolo styles, then dont try to play on the looser section of string cause it can be difficult.
I usually dont play over the pickups but usually in between the 12th and 22nd fret. If you pick at the halfway point of the string, between where it is fretted and to the bridge then you will get the thickest tone, and if you play at either end, then it will have more of a "ping" sound, kinda twangy.

anyways i have babbled enough.