Not sure if you're looking for a leading role in a film, because I'd say the one I've got in mind had him as a supporting actor - albeit a very significant support! 'The Untouchables' in which he played Al Capone to Kevin Costner's Eliot Ness. A brilliantly staged film full of memorable sequences.
First, there's the opening scene in which Capone holds court to journalists whilst having a shave in a barber's shop. Then the barber accidentally cuts him. Capone magnaminously forgives him after a moment of stunned silence, but the look of terror on the barber's face says it all about Capone's reputation!
Then there's the scene where there's a gathering of gangsters who are all supposed to be loyal to him, and DeNiro talks to them as he walks around the table with a baseball bat - no prizes for guessing what he eventually does with the bat! A great, shocking display of malevolence in a great film full of great performances besides DeNiro's.