The main feature that distinguishes a prokaryotic cell from a eukaryotic cell is the absence of a nucleus in prokaryotes. Prokaryotic cells, which include bacteria and archaea, have their genetic material located in a region called the nucleoid, without a surrounding membrane. In contrast, eukaryotic cells, found in organisms like plants and animals, possess a well-defined nucleus that houses their DNA, along with various membrane-bound organelles that perform specialized functions.