This is one of those things that is not only personal preference, it has to do with a whole mess of other factors like which knife (as in whether it has an opening hole, thumbstud, push button, index trigger, etc.) as well as the size of the knife. Also it has to do with what kind of pockets you have and which pocket you keep it in (front, rear, etc.), where you keep it in the pocket (towards the seam, away from the seam, etc.), how coordinated you are, and I think a huge factor is how your hands are. My fingers are a bit stubby so if I'm carrying a tip up when I go to grab my knife my thumb is nowhere near the opening mechanism on a knife that is around 3.25". If it was the size of a Kershaw Chive (if the Chive was tip-up) then I would have no problem, but on something like the LCC then I'd have a real problem with deployment. I had my LCC converted to tip-down so you know what my preference is.
This topic comes up all the time and it will continue to come up because we can never all agree on what's "best". You should always read up and see the advantages/disadvantages, but in the end you still have to make the decision on your own and probably the only way to do that is to go out and try it yourself. I've tried both ways and I picked tip-down. Don't care that other people insist that tip-up is the only way to go--it just doesn't work for me.