A modeling method of multi-objective optimization design for parallel mechanisms (PMs) is proposed, whose implementation is illustrated with 2RPU-RPS mechanism as an example. The orientation of biased output axis on moving platform is depicted by spherical attitude angles, and its kinematic model is deduced through vector method. With screw theory as mathematic tool, a comprehensive evaluation method of kinematic performance for PM is established. On this basis, the expensive constrained multi-objective optimization model of dimensional parameters for the discussed mechanism is constructed. The NSDE-II algorithm, formed by replacing the genetic algorithm operators in non-dominated sorting genetic algorithm II (NSGA-II) with DE operators, is utilized to solve this multi-objective optimization problem, thus obtaining multiple Pareto optimal solutions with engineering application significance, which proves the feasibility and effectiveness of the proposed modeling method and algorithm. Moreover, the normalization coverage space and the minimum adjacent vector angle are proposed to evaluate the computational performance of NSDE-II. Finally, the potential engineering application value for the optimized 2RPU-RPS PM is presented.