Reverse shoulder arthroplasty biomechanics can be improved by modifying the placement of prosthesis. Biomechanical studies have quantified the impact of placement modifications on the mobility and stability of the reverse shoulder. While these studies have provided detailed insights, direct comparisons between their finding are obfuscated by their use of differing methodologies. The aim of our study was to develop an assessment framework which used musculoskeletal simulations to consistently evaluate the biomechanics of various placement modifications. We conducted musculoskeletal simulations of humeral elevations and rotations using 15 reverse shoulder models. For each model, these simulations were conducted for a reference configuration of the prosthesis, established using surgical guidelines, and 34 modified configurations, which were based on commonplace adaptations to the placement of the glenosphere and humeral tray. The effect of each modified configuration on deltoid elongation, deltoid moment arm (DMA), joint stability, and impingement-free range of motion (IFROM) was determined relative to the reference configuration. We found that 16 of the 34 modified placements had an overall beneficial impact on reverse shoulder biomechanics. Within this subset, we identified two biomechanical trade-offs. First, there is an antagonistic relationship between IFROM and both the DMA and joint stability. Second, functional requirements differ between humeral elevations and rotations. Furthermore, we found that posteromedial translation of the humeral tray had the most beneficial impact on joint stability and inferior translation of the glenosphere had the most beneficial impact on IFROM and DMA.