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I'm "the enemy" ... ie an Obama supporter from the start ... but I agree with your assessment of the landscape. This is a Godfather move, no question.
However, I disagree when you say that the SoS position takes her out of the mainstream, or that working for Obama makes her irrelevant. I don't see foreign policy becoming irrelevant anytime soon, and anyone who thinks so doesn't remember, oh, six months ago.
Hillary Clinton lost the primary because she refused to use the fifty-state strategy. She could have ... she was advised to ... but she didn't take any of her opposition seriously enough to go that way. It was a simple miscalculation, and thems the breaks.
She's a brilliant and talented lady. Whether or not she stays relevant depends on her ... either as a senator, or as Secretary of State, or as future Governor of New York or in some other capacity entirely.