The major issue I've heard people take with this is that MacFarlane doesn't have the "street cred" to go into serious TV. When people see "Seth MacFarlane", they think "Family Guy", much like when people see "Leonard Nimoy", they think "Mr. Spock". That said, however, if MacFarlane can make it work, then I'm all for it.
The question is - what the hell would it be about? Where would it be set?