Hi John, yes it does matter a bit although depending on the application you could render the effect pretty minor or zero.
Primaries are usually at the front, and Holley carbs designed to be used in competition usually have fuel control measures designed to combat fuel slosh generated in that particular orientation. Primary and secondary fuel bowls have slightly different site plug heights for setting float levels and sometimes fuel bowl baffling is only on the secondary bowl to stop a rich stumble under brakes. If you paid a bit of attention to replicating the original fuel slosh management measures with the carb at flipped 180 degrees and jetted it specifically for that orientation you'd probably be fine.
The only bit I'm not sure about is mixture distribution at cruise if you had something like a Performer or Performer RPM intake manifold. Dual plane intakes are a wee bit compromised in terms of mixture distribution by design, and will be designed to have wet fuel/air emulsion added at the front in light throttle and cruise situations. Less of a consideration in an open plenum design.
Cheers, Andrew