Steve,
Firstly it is necessary to determine the analysis and response before we optimize.
You really need to define the analysis type, the load does vary with frequency from what I see, you need to determine what loads to apply and how it varies with the frequency, this is the essence of vibration analysis.
It is simple to determine certain regions as design and non design, however the model must reflect the structure as it is in reality and it must be joined with elements representing the structure, it is not understood by the solver unless it exists as elements.
When you are sure you have identified the analysis, you then need to identify the type of optimization. have you seen the below tutorial?
Altair OptiStruct > OptiStruct Tutorials and Examples > Tutorials > Topography Optimization:
OS-3030: Random Response Optimization
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