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You should use the default plugin's which are set to use high-end moderate hardware by default, use the GSdx graphics plugin, and set the resolution to a 4:3 ratio (1280 x 1024 is good) for best performance, make sure u enable multi-core in the CPU options, however do know that there isnt a BEST configuration, you have to try different things and see what works best for your computer
 
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