I think I've figured out what it is that makes Seth MacFarlane "hard to take" as a persona. I mean "overall," of course - whether he's not your cup of tea because of the subject matter of his humor (or choice of target) is another matter entirely. I'm talking more about why even I, as someone who thinks he's a real comic talent, can agree that a little of him goes a long way:
He's just a little too conventionally-handsome, a little too well spoken and a little too outwardly-confident about it for a comedian.
A modern comedian, anyway. His only semi-ironic affection for the Rat Pack era of lounge-act emcees makes an alarming amount of sense when you consider how well his look, delivery and sensibility would fit in that milieu; i.e. in the era where The Entertainer was The Alpha of the room, with the audience and (especially) "The Other" as his lessers to be humorously judged. The main difference is target: Frank & Dean basked in their superiority over both "squares" and (explicitly at first, implicitly later) the "lower" classes/races, while MacFarlane works basically the same act (right down to the "you think I'm smug now, just wait till I back it up with these pipes!" shift to songman) but with Middle America and/or religious-conservatives as the targets of choice. He's a completely different animal from the self-effacing post-60s face of modern comedy, for better or worse, save that he shares their penchant for self-hate... it's just that he seems to hate his advantages instead of his foibles.
Case in point: The new trailer for "A MILLION WAYS TO DIE IN THE WEST," his Western-spoof follow-up feature to "TED," which features MacFarlane as his own lead in full-on Brian Griffin only-smart-man-in-a-world-of-morons smug mode and also in full-on Brian Griffin douchebag-who's-too-happy-about-being-the-only-smart-man smarmy mode; but here as a snarky Eastern transplant in The Old West cursed with a modern eye-view of the horrible shittiness behind the myth of the Cowboy Era. Looks funny, but I also remember how "WAGONS EAST" failed to stretch the same basic joke to feature-length...