Depends on the mood I'm in and who it is. Usually if it's a salesman I can say no easily. With friends it's a lot more difficult. I don't like hurting their feelings, I don't like coming over as mean, and I want to get them what they want.
Actually it's not often necessary to give a categorical yes or no. I often forget this in the heat of the moment, but answers such as "Can I think about it?" "Maybe. It depends on....." or "I'll try, but I'm not promising anything" are often much better. Even if you can't give somebody what they want, you can usually at least throw them a scrap of some kind.
It bothers me a lot when I simply can't get them what they want.......I instinctively want to tell them the plain truth, that the answer has to be no because of the logic of the thing, but instead I often try to help in ways that I know are very unlikely to work, just to make sure that they won't think I didn't care.
In the workplace it can be a more difficult problem. There, you may be dealing with a greedy person who can take away your livelihood if you don't help them to exploit you. It helps to know your rights, but there's a grey area where nobody knows if you can say no or not.