While I think missions can be very useful in providing structure to a new player's game, there is always the feel that you're in some sort of binding contract you never agreed to.
I was just playing Anno 2070 the other day, got a mission I didn't want to do, ignored it, and was sent back a soundbite that when something along the lines of "You lying cheat!"
I mean, I never agreed to anything. How am I a liar or a cheat?
It really should go something like "If you have the time, we'd be really like you to get this done. There's money in it for you if you do, but no real consequence if you don't."
That always seemed like something you'd ask the supreme ruler of your nation, not "DO THIS OR I THROW A HISSY FIT."
So long as the mission giver is capable of respect and civility, I'm for domestic missions.
Otherwise, it is a firm negatory.