The main characteristic that distinguishes a prokaryotic cell from a eukaryotic cell is the absence of a nucleus and membrane-bound organelles in prokaryotic cells. Prokaryotes, such as bacteria and archaea, have simpler cell structures, with their genetic material localized in a region called the nucleoid. In contrast, eukaryotic cells possess a defined nucleus that houses their DNA and various organelles that perform specialized functions. Understanding these differences is crucial for studies related to cell biology, evolution, and microbiology.