Here's a few possible reasons:
-If they're on cL, the Section Modulus of the Bolt group is better for loading on cL [i.e., lower "extreme" fiber stress for horizontal/vertical moments]
-Easier to scribe a centerline if there's no hole in the way
-It will fit to everybody else's piping, since they straddle cL's. Most Standard Fittings, Valves, etc., have bolt quantities in multiples of 4, & straddle cL's.
Flanges on valves, pumps, turbines, heat exchangers, etc follow this convention. That's why pipefitter's "two-hole" flanges when fitting-up. Typically, the pipe being worked on is horizontal, in stands or a tri-stand, and levelled, if welding. Flanges being installed by whatever joining method are oriented such that studs or bolts inserted in the top two holes (the flange face being vertical) are true horizontal when a level is laid across them. Since flange bolt holes are symetrical, the holes will line up when it's time to join things together.
Another reason is the increased resistance to bending of the pipe that results. With the bolts stradelling the centerline, you now have (2) bolts supporting the weight of the pipe/fluid and resisting the moment that is trying to open up the flanges.
