Here is what I think:

1) If it is a fairly large website, then first get the core on paper, then fireup the Omnigraffle, sketch some initial screens in to it, and see if it make sense regarding flow.

OR

2) If it is not that big website, then starting with Twitter Bootstrap Framework will do the job.

See the thing is "what is the only I should do the wireframe", the real question is "What's the demand of the situation and context?"