Does the EPA have a list of the nation's major environmental issues?
The US EPA mandate is quite broad as are the range of environmental issues. The issues aren't really amenable to such a list because it is subjective to decide what is 'major' except in very broad terms. Major could mean greatest risk or it could mean of greatest importance to address soon. Those could be different things, for example, carbon dioxide emissions are high risk but difficult to address whereas an industrial site with leaky chemical drums might have only a local risk but need dealing with right away to contain the problem.

The 'Learn the issues' tab gives the important areas in a general sense; you could look at the EPA organisation chart to see where they are putting their resources.

For the specific case of pollution from old industries, The Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA or Superfund) maintains the National Priorities List (NPL) for sites needing cleanup.