(written from a Production point of view)
In 2004, he used his pseudonym Simon Judas Raye when he provided the Guardian's voice for the fan-made internet series Star Trek: New Voyages episode "In Harm's Way". The episode features Trek performers James Cawley, Jeffery Quinn, Barbara Luna, William Windom, Malachi Throne, and Leslie Hoffman with John Carrigan and was written by Doug Drexler.
Witwer is fan of Star Trek: The Original Series, Star Trek: The Next Generation, and Star Trek: Deep Space Nine. In one Tweet, Witwer called on CBS to remaster DS9.   He is also listed as a contributor for the documentary What We Left Behind. 
He previously guest-starred along with Star Trek: Voyager actress Roxann Dawson (B'Elanna Torres) in an episode of The Lyon's Den called "Duty to Serve"; Leland Orser also guest-starred in this episode. In 2005, Witwer guest-starred in the pilot episode for the short-lived series Inconceivable, along with Casey Biggs and Alfre Woodard. He went on to play the recurring character of Lt. Crashdown on Ronald D. Moore's re-imagined Battlestar Galactica television series.
His other television credits include guest-spots on ER, JAG (2001, with Robert Pine), She Spies (2002, with Ray Wise), NCIS (2004, with Scott MacDonald), and Cold Case (2004, with fellow ENT guest stars Robert Rusler and John Mahon).
From 2008 to 2009, he portrayed Davis Bloome/Doomsday in the Superman series Smallville (which featured appearances by John Glover and Phil Morris) and appeared as a social worker in the science fiction thriller Game (2009, with Henry Hayashi). Witwer is also the head of the band "The Crashtones" which released an album in 2006.
Best known for his work in Star Wars, in 2008, Witwer portrayed Darth Vader's secret apprentice, Galen Marek (codename Starkiller), as well as the voice of Emperor Palpatine (who in his first on-screen appearance in The Empire Strikes Back had been voiced by Clive Revill, though his scenes were removed when the sequence was reshot for the DVD release in 2004), in the multimedia project Star Wars: The Force Unleashed, and reprised the former role in Star Wars: The Force Unleashed II two years later, providing both his voice and likeness to the game's lead character across all of the media; in both games, Cully Fredricksen portrayed Starkiller's mentor, Rahm Kota. Since 2012, Witwer has provided the voice of Darth Maul in almost all Star Wars media, most notably the TV series Star Wars: The Clone Wars and Star Wars Rebels, and the film Solo: A Star Wars Story. Witwer voiced the lead character in 2019's Days Gone (being joined in the cast by Daniel Riordan and Phil Morris).
Witwer is also a player of Star Trek Online; when Kenneth Mitchell was unable to voice Tenavik in the game's 11th anniversary update in January 2021 (due to the progression of his ALS), he personally chose Witwer as his replacement.