It's kind of bugging me to see reviews state that Macfarlane "bombed" with the theater audience. I rewatched the opening and they were laughing their asses off, and were with him through much of the night.
And even the shocked reaction to his John Wilkes Booth joke was exactly the kind of response you're looking for with a joke like that.
Joan Rivers was on Stern this morning and brought up an interesting point. Billy Crystal once said to her that hosting the Oscars was really tough for any host as the night went on because more and more people in the audience were upset at losing with each award.