The settings that Blender starts off with is immensely important to the user experience. The less the user has to set up to get going, the less friction he/she will face when getting started. Having sane, useful defaults benefits both new and experienced users.
If you have to fiddle with less options to get Blender into a useable state you get benefits for both.
New users: Can start to learn faster
Experienced: Can start to create art faster
So, how do we determine which defaults to set? We can use the 80/20 rule (http://en.wikipedia.org/wiki/Pareto_principle). This means making sure Blender's defaults fit with 80% of the things people will be doing.
Units: Metric (makes your 3D scene relate to reality. It's a useful starting point. '2.000' means nothing to users, but '2 meters' or '2 kilometres' does)