This paper studies the effect of rotor blade aerodynamics and rotor grouping on the accuracy of open-loop simulations with respect to generated trajectories and energy consumption for multi-rotor drones. To examine these effects an 18-rotor high performance drone carrying a 30 kg payload is used. The effect of the rotor blade aerodynamic model on simulation results is examined by comparing roll, pitch, yaw, and vertical motion trajectories produced when using blade element theory model with trajectories produced when using a lumped blade model. The results show a 20% difference between the maximum roll and pitch angle achieved, a 58% difference in maximum altitude achieved, and a 91% percent difference in the maximum yaw angle achieved. These results indicate that the choice of aerodynamic model for the rotor blades has a significant effect on the simulated trajectories and in the calculated energy consumption of those trajectories. The effect of rotor groupings on energy consumption is examined by comparing two different rotor groupings for the 18-rotor drone. Roll, pitch, and yaw motions are simulated for both groupings and the resulting energy calculation shows a 4–5% difference in energy with a motor efficiency curve and a 8–9% difference with a motor efficiency curve included in the power calculation. These results indicate that rotor grouping is important in over-actuated drones for reducing the overall energy consumption of the drone, and thus increase its endurance. This energy reduction may become especially important when closing the loop with a control system or in extreme flight conditions such as stall or strong gusts.