It is my personal belief that a carry gun should definitely have a round in the chamber. To me, chambering a round while the threat is present only increases reaction time, increases steps you need to take to address the threat, and increases the things that could go wrong. I see no advantage to carrying what, to me, is essentially an unloaded gun.
As to the safety, I think that has a lot to do with how much practice and muscle memory you create in swiping it off, the type of firearm you carry, and your mode of carry. However, I'll let folks who carry guns with safeties provide more details and experienced input. Personally, I'm a fan of keeping the steps to engage the threat at a bare minimum. I'm a fan of simple and effecient; for that reason, I carry a pistol with no external safety to disengage. My Glock (insert any similar pistol and all revolvers that I can think of) is draw, aim, shoot with no extra steps. Other opinions may vary.