Compton cameras have been used for astronomical and medical imaging applications as early as the 1970s. Recent interest in their potential for the detection and localization of special nuclear material (SNM) has led to increasing investigations. In this work, a specialized algorithm was developed for the optimization of a two-plane Compton camera. The MCNP-PoliMi code was utilized to simulate photon interactions within the detectors and coupled with an analytical technique used to estimate angular uncertainties. Using our specialized algorithm, a large area (approximately 1 m2) Compton camera consisting of two planar arrays of photon detectors was evaluated for several scintillators: LaBr3, CaF2, NaI, and plastic (C9H10). Optimization of plane thickness and voxel size were conducted for Compton camera efficiency and angular uncertainty at source energies of 100-400 keV.