Unless specifically noted otherwise by the piping designer (and then only if for good reason) all flange bolt holes shall straddle the "natural" centerlines. This is the flange bolt hole orientation rule. This "natural" centerline rule for flange is known, understood and followed by all responsible equipment manufacturers and pipe fabricators.
For a vertical flange face (the flange face in vertical and the line is horizontal) the bolt holes shall be oriented to straddle the vertical and horizontal centerlines.
For a horizontal flange face (the flange face is horizontal and the line is vertical up or vertical down) the bolt holes shall be oriented to straddle the (plant) north/south centerlines.
Care must be taken to check all equipment vendor outlines to identify any flange orientations that do not match this rule. When an exception is found the vendor can be requested to change his bolt hole orientation. This is not always successful and if not then the piping designer must insure that the piping fabrication documents call for the correct orientation.
This rule of bolt holes straddling the natural centerlines is sometimes referred to as "Two-Hole" the flange. This means that the two of the holes straddle the centerline. To "One-Hole" a flange means that the flange has been rotated so that one hole is right on the natural centerline. I assure you that 99.999% of the time that to "One Hole" a flange is a mistake and will add cost to the field. It also makes the piping foreman very unhappy.