To me, and from the posts I read it really depends on how and where you carry the knife. If you carry in a front pocket towards the back, then tip up would make sense, because reaching into your pocket you are going along the spine, and the pocket lining helps hold it shut. If you carry in a back pocket, tip down is probably safer, because there is nothing to keep the blade closed except gravity. Generally, I would say it is hard to argue that tip up is safer than tip down. It could be faster, etc. But keeping the pointy end away from the direction of your entering hand is hard to beat for safety.
Regarding the ergonomics, it also depends on where you end up deploying it. With the tip up, your hand is already aligned with the open position of the knife, and it can be easily deployed with the hand right out of the pocket. Although for knives that sit deep in the pocket, you typically have to adjust the grip once it is out to be in the best position. However, particularly if you are in a front pocket with a tip down knife, when you pinch the top of the knife to pull it out, you can have the wrist already turned forward and the knife easily rests in place as the arm comes up. So here it depends if you pull the knife out wrist straight or wrist bent.
So, to me, deep pocket carry knives should be tip down almost always for fast deployment. Knives that ride a little higher can deploy in less motion if they are tip up.
Now, the trick for me is that as a left hander, most knives aren't optimized for me anyway. So, for my tip up Kershaw Ti-34 I carry it in my back left pocket, with the blade spine against the pocket seam.
With my Benchmade mini - Stryker which is tip down, I carry it in the front pocket, with the assumption (after some practice) that I'll end up in reverse grip on it in a speed sensitive situation. With my Microtech mini - Socom, I use the horizontal carry pouch. When possible though, I generally carry a small fixed blade I made in a knife making class - tip down, sits low on the belt, with the point of the sheath in my back left pocket.