Variability in motor rehabilitation program outcomes can be attributed not only to individual components (human patient/rehabilitation equipment) but also to their system-level interactions. Thus, effective deployment of a rehabilitation program depends upon: 1) suitable therapist selection of user-device ergonomics; 2) adjustable device settings; and 3) exercise regimen parameters; to achieve desired system-level motor performance. In this paper, we discuss aspects of creation of a virtual design environment, leveraging tools from musculoskeletal analysis, optimization, and simulation-based design, to permit therapists to rapidly evaluate and systematically customize rehabilitation programs. Specifically, this framework is intended to facilitate 1) parametric study of ergonomic/device/regimen settings on musculoskeletal performance; 2) use of design tools such as optimization for decision support in arriving at the best program; and 3) scaffolded examination of linkage between form and function by iterative what-if type of analyses. We use two case studies (bicep-curling and motor rehabilitative driving) to highlight benefits of such simulation-based rehabilitation program evaluation.