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More background is needed. If the system is linear then you can drop in 3 orthogonal direction then use linear superposition to determine the worst angle. I hope this helps.
You can usually do it by inspection: In which direction will the response be the stiffest?
What is the stiffest direction to drop a car? If you are interested in seat design my above method would possibly be appropriate. If you are looking for external structures such as the hood or windows it would not and you would have to use an optimization method varying angles trying to minimize the FOS. I hope this helps.