The greatest paper map of the United States I've seen is not this one (though I ordered this one), it is "USAtlas" created by Richard Saul Wurman using early Macintosh design tools like Adobe Illustrator 88 and Aldus PageMaker 3.02 on a Mac Iici.
Wurman is cited in "Building Legible Cities 2 Making the Case" and, oh yeah, created the TED conferences.
The biggest innovation for me as a frequent long distance driver in the late 80's and early 90's was having every page the same scale. But the clarity of information on a given page or city was unprecedented, was easily glanceable while driving, and is still unmatched to this day though Google Maps' data view comes close while offering more details. But this was hand drawn.
Here's Cincinnati. Notice the state borders vs rivers:
Wil Tirion plots star maps. At one stage he was using Illustrator on a Mac. Graduated from a drawing table and Rotring pens. I find his maps easier to use in the field than a laptop or netbook with 'red screen'. Its the overview aspect I suppose.
Quite a lot of published maps pass through Illustrator or similar at some stage for careful human retouching and intervention. For larger scale (quantity, not map scale) stuff then you tend to have a source data set containing the raw geospatial data and feed that through a series of processes to handle styling, annotation placement and white space management, and even division into map sheets.
Engineering maps tend to be generated far more directly from the source data, and as the quality of things like Google maps improves it gets harder and harder to meet people's cartographic expectations without human intervention.