De Niese's career has ranged through Baroque music (Poppea in "L'incoronazione di Poppea"), via Handel, Mozart and contemporary opera premieres ("RAAFF" by , 2004, De Nederlandse Opera) at major opera houses around the world, to Broadway ("Les Misérables") and film ("Hannibal") roles. She has appeared in productions of a number of Baroque operas on stage and on DVD, including the Les Arts Florissants production of "Les Indes galantes" by Jean-Philippe Rameau, and as Cleopatra in "Giulio Cesare", directed by David McVicar, at Glyndebourne in 2005, 2006 and 2009, and in the same production at the Lyric Opera of Chicago in 2007.