Reconfigurable structures based on origami design are useful for multifunctional applications, such as deployable shelters, solar array packaging, and tunable antennas. Origami provides a framework to decompose a complex 2D to 3D transformation into a series of folding operations about predetermined foldlines. Recent optimization toolsets have begun to enable a systematic search of the design space to optimize not only geometry but also mechanical performance criteria as well. However, selecting optimal fold patterns for large folding operations is challenging as geometric nonlinearity influences fold choice throughout the evolution. The present work investigates strategies for design optimization to incorporate the current and future configurations of the structure in the performance evaluation. An optimization method, combined with finite-element analysis, is used to distribute mechanical properties within an initially flat structure to determine optimal crease patterns to achieve desired motions. Out-of-plane and twist displacement objectives are used in three examples. The influence of load increment and geometric nonlinearity on the choice of crease patterns is studied, and appropriate optimization strategies are discussed.