External Frame Buffer should be Disabled. Anti Aliasing and Anisotropic Filtering should be set to none for max performance, my GPU cannot handle AA but it can handle AF at 16x with no frame loss. You may increase this until you notice your frames drop. My GPU is capable of running at 4x Native with no frame loss and it proves to be a much much better image resolution. OpenGL will be better on most NVIDIA GPU's when you enable Vertex Streaming Hack under the Hacks tab. The best one will differ depending on your computer. Ensure that you have a Standard Controller under port 1 and the rest are nothing (unless somebody else is plugged into your computer). This is if you want to play melee netplay just incase.
Make sure all wiimotes are set to NONE.