I alternate picked for years, and about half a year ago I made the switch to directional picking and I really like it.

Anyway, I've noticed that I am much more comfortable going up the strings, 1st to 6th, than I am going down. The reason is that I've developed the habit of angling the top of the pick toward me when coming up to facilitate easier string changes, but when I go down the strings it's more difficult to do this and maintain proper muting technique.

So the question is: should I be angling my pick slightly in the direction I am going, or should I be aiming to keep it as upright as I can regardless? Any of you directional pickers have a preference?
Shawn Lane tilted his pick upwards regardless of the direction he moved. Paul Gilbert tilts his downwards I believe. Downward tilt seems to be more common but you can find examples of both all over the place in any case.

I've never seen anyone alternate between the two tilts while playing. Find the method that is most comfortable for you and stick with it.
I've found it doesn't matter all that much to me. Sometimes it's tilted. Sometimes quite straight. Sometimes the pick is angled to the strings. Sometimes flat.

What might be more important is the grip. I've noticed during the down stroke, almost all the pressure is applied by thumb, upstroke by finger. Overall grip is fairly light.

That's just based on a quick analysis. I haven't considered it in detail really. But I do recall I change angles all the time. More for effect than ability to control the pick.