This really depends on the knife, the pants, and what else I'm carrying. I prefer tip-up in a front pants pocket. If my front pockets are full, I will sometimes carry on the closest edge of a back pocket. The knife needs to be relatively flat or straight, with a deep-carry clip, and a reasonably strong detent. The only possible issue is that I prefer tip-up there too and the opening side is not against a seam. In theory, the knife could open into the pocket but it hasn't happened yet.
With the right knife, I also like tip-down in a shirt, breast, or vest pocket. The M390 Dividend with deep-carry loop-over has been amazing with heavier dress and work shirts.