The lesson of Republican senator Gregg changing his mind about being Obama's Commerce Secretary is pretty clear to my mind. He knew what Obama's intentions were, what Obama's pragmatic policies would be, where Obama was coming from. Yet he still agreed to take the job.
Yesterday he changed his mind. At first he said it was because there were irreconcilable differences between Obama and him in terms of policy. But after it became known that he obviously knew all along what Obama's policy ideas were and had agreed that he could work with them, he came back with a different excuse, that he just didn't feel comfortable leaving the Senate (where his vote is crucial given the small margin the Democrats have which makes it possible for the Republicans to virtually block any bill they are united against).
I think what happened is, it became crystal clear that his fellow "conservative" (i.e. rightwing) Republicans weren't going to go for any "bipartisan" overtures, but instead were going to play the old Gingrich obstructivist game with Obama, no matter how far he bent over backwards to accommodate them and their demands (i.e. making tax cuts way too big a part of the stimulus bill and spending on the poor and education etc. way too small, and making those tax cuts a little less beneficial to working people and a little more so for corporations and the wealthy).
Gregg decided to do what they did: add to Obama's challenges. Maybe he doesn't wish the Obama administration ill, as others of his fellow Republicans have made clear they do (Rush's famous public statement that he wants Obama to fail, which means he wants the country and our democracy to fail since Obama was elected by us to carry out the policies he presented in the campaign and because the dire economic situation Bush Junior led us and the rest of the world into impacts the future of our country). But Gregg obviously also doesn't want the possibility of being replaced by a more moderate Republican (by the Democratic governor of his state) who might side with the only three Republicans who were willing to make a bipartisan compromise on the stimulus package.
The lesson for Obama seems clear to me. Don't try to play nice with rightwing Republicans (which currently means almost all Republicans in the House and Senate), because they don't play nice, and never have. They are out for power for themselves and the destruction of anyone or anything that would keep them from it. Hopefully their tactics are transparent enough to voters that in the midterm elections they'll lose even more seats and finally be the miniscule minority they deserve to be after what they've done to this country (i.e. during their turn in power that created most of the problems Obama faces).