Mapnik can be used in a variety of ways. The most widely used options are using XML config files, using the Python bindings or using the API directly in C++.
To get first results, choose your weapon: XML, Python, C++, node.js, Ruby, Java (last two are less complete)
Generating Contours - Using Mapnik with GDAL to build contours of the world.
ManagingLargeXmlFiles -- Do things once and only once using XML entities.
MapnikReferences -- Various other resources related to Mapnik and Mapping