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Currently, nearly everyone separates in Photoshop by doing >Edit>Convert to Profile... and it doesn't seem that many people have given this process any thought. While one profile may work pretty well most of the time, no one profile can meet all rendering needs, even for one press condition.

I used to believe in a correspondence model of separating: the goal was to match the RGB. My goal now is to beat the RGB. To that end, for certain kinds of pictures I'll use software which is pre/non-ICC based. I never separate without thinking about the use and the meaning of the picture, and what else I can do for it by carefully converting. Moreover, changing spaces gives often absolves the picture of its previous difficulties.