The crash safety of lithium-ion traction batteries is a relevant concern for electric vehicles. Current passive safety strategies of traction batteries usually come at the cost of their volumetric or gravimetric energy density. This work analyses the influence of the variables cell selection and orientation within the traction battery on the crash safety of an electric-powered two-wheeler. These two variables do not negatively influence the traction battery’s volumetric or gravimetric energy density in the design process. Metamodels and numerical simulations are used to evaluate the crash safety of an electric-powered two-wheeler’s traction battery in a potentially dangerous crash scenario. The influence of the variable’s cell selection and orientation is evaluated through the internal short circuit risk of the integrated cells. The comparison of the metamodels shows that the cell orientation reduces the internal short circuit risk by up to 51% on average in the analysed crash scenario. The cell selection reduces it only up to 21% on average. The results show that crash safety can be increased in the design process, and a combination with the current protection strategies can increase crash safety further.