HVAC Supply and Return Re-routing
Depending on where you live, yes, moving the return air duct can affect the efficiency. 

If you “heat” mostly each year, then the efficiency of the unit is increased if the return air grille is located at a high point in house. This allows the unit to return the “warmest” air to the unit, it reheats that air and then redistributes it throughout the house. 

If you move the return air to a lower position, cooler air will be returned to the unit and therefore need to be heated more before redistributing it throughout the house. 

Likewise, if you cool your house more each year, the location of the return air can increase its efficiency by relocating it to a new location. 

BTW, one reason the SUPPLY ducts are run directly to the attic is because they can be “run” to each room easily in the attic. 

Back when we all had radiators and baseboard heat, we liked them to be installed low so the heat radiated and rose up (often drying out condensation on single pane windows). Now, we can “push” air so vents don’t need to be “low”. In fact, having a dresser on a vent opening will greatly reduce its effectiveness.