Digital microfluidics is a popular tool for lab-on-a-chip applications and is typically implemented in one of two formats: single-plate (“open”) devices or two-plate (“closed”) devices. Single-plate devices have some advantages relative to the more common two-plate format such as faster mixing, the capacity to move larger volumes on a given footprint, and easier access to droplets for handling or optical detection. In contrast with the two-plate format, in which ground potential is generally supplied via a top electrode, in the single-plate format, many different geometries of ground wires/electrodes have been used. Until the present study, there has been no metric to determine which of these geometries is best suited for droplet actuation. Here, we present a combination of numerical simulations and experimental tests to compare six different single-plate designs. We applied finite element analysis, using the commercially available COMSOL software package to calculate the electrodynamic actuation forces in each of the different designs and used the results to optimize device design. Forces predicted by the electrodynamic model were in agreement with forces predicted using electromechanical models. More importantly, results were verified experimentally using a unique technique that permits indirect estimation of actuation forces on digital microfluidic devices. This work illustrates the promise of using numerical modeling to enhance the design and performance of digital microfluidic devices.