Patrick Stewart first played Charles Xavier / Professor X in X-Men (2000) and reprised the role in subsequent Fox X-Men universe films featuring the character. He reprised the role in Doctor Strange in the Multiverse of Madness (2022), which is an MCU film.
Tony Curran played Priest in Blade II (2002), Man in Black Agent in X-Men: First Class (2011), Bor Burison in Thor: The Dark World (2013), and Finn Cooley in Marvel's Daredevil (2015) S02E04 "Penny and Dime".
Leonor Varela played Nyssa in Blade II (2002) and Camilla Reyes in Agents of S.H.I.E.L.D. (2013) S01E02 "0-8-4".
Bruce Campbell played different cameo roles in Sam Raimi’s Spider-Man trilogy: Ring Announcer in Spider-Man (2002), Snooty Usher in Spider-Man 2 (2004), and Maître d’ in Spider-Man 3 (2007). He also voiced the Tutorial Guide in the video games based on the same films, as well as the Xtreme Reporter in The Amazing Spider-Man (2012 video game). He played Pizza Poppa in Doctor Strange in the Multiverse of Madness (2022), an MCU film also directed by Sam Raimi.
J.K. Simmons portrayed J. Jonah Jameson in Spider-Man (2002), Spider-Man 2 (2004), Spider-Man 3 (2007), and Venom: Let There Be Carnage (2021). He reprised the role of J. Jonah Jameson in Spider-Man: Far From Home (2019) and Spider-Man: No Way Home (2021), which are MCU films. He voiced J. Jonah Jameson in Spider-Man: Across the Spider-Verse (2023).
Tobey Maguire played Peter Parker / Spider-Man in Spider-Man (2002), Spider-Man 2 (2004), Spider-Man 3 (2007), and reprised the role in Spider-Man: No Way Home (2021), which is an MCU film.
Willem Dafoe played Norman Osborn / Green Goblin in Spider-Man (2002), Spider-Man 2 (2004), Spider-Man 3 (2007), and reprised the role in Spider-Man: No Way Home (2021), which is an MCU film.
Jon Favreau played Franklin "Foggy" Nelson in Daredevil (2003) and then Happy Hogan in Iron Man (2008) and reprised the role in subsequent MCU films featuring the character.
Alfred Molina played Otto Octavius / Doctor Octopus in Spider-Man 2 (2004), and reprised the role in Spider-Man: No Way Home (2021), which is an MCU film.
Patton Oswalt played Hedges in Blade: Trinity (2004), the five Koenig brothers in Agents of S.H.I.E.L.D. (2013), as well as Pip the Troll in Eternals (2021). He also voiced M.O.D.O.K. in Marvel's M.O.D.O.K. (2021 stop-motion animated TV series).
Ryan Reynolds played Hannibal King in Blade: Trinity (2004), Wade Wilson / Deadpool in X-Men Origins: Wolverine (2009), Deadpool (2016) and Deadpool 2 (2018). He will reprise the role of Deadpool in Deadpool 3, which is an MCU film.
Laurence Fishburne voiced the Silver Surfer in Fantastic Four: Rise of the Silver Surfer (2007), played Bill Foster in Ant-Man and the Wasp (2018), and voiced the Beyonder in Marvel's Moon Girl and Devil Dinosaur (2023).
Thomas Haden Church played Flint Marko / Sandman in Spider-Man 3 (2007), and reprised the role in Spider-Man: No Way Home (2021), which is an MCU film.
Tim Blake Nelson played Samuel Sterns in The Incredible Hulk (2008) and Dr. Harvey Allen in Fantastic Four (2015). He will reprise his role as Samuel Sterns / the Leader in Captain America: New World Order (2024).
Clancy Brown voiced Mr. Sinister in Wolverine and the X-Men: Foresight (2009), voiced Taskmaster in Iron Man & Captain America: Heroes United (2014), played Ray Schoonover / "the Blacksmith" in Marvel's Daredevil (2015), and voiced Surtur in Thor: Ragnarok (2017).
Djimon Hounsou voiced Black Panther in Black Panther (2010 animated TV series) AKA Black Panther: Who is the Black Panther? He then played Korath in Guardians of the Galaxy (2014) and Captain Marvel (2019).
Olivia Munn played Chess Roberts in Iron Man 2 (2010) and Betsy Braddock / Psylocke in X-Men: Apocalypse (2016).
Idris Elba first played Heimdall in Thor (2011) and reprised this role in subsequent MCU films featuring the character. He also played Moreau in Ghost Rider: Spirit of Vengeance (2011).
Colm Feore played Laufey in Thor (2011) and Donald Menken in The Amazing Spider-Man 2 (2014).
Andrew Garfield played Peter Parker / Spider-Man in The Amazing Spider-Man (2012), The Amazing Spider-Man 2 (2014), and reprised the role in Spider-Man: No Way Home (2021), which is an MCU film.
Rhis Ifans played Curt Connors / Lizard in The Amazing Spider-Man (2012), and reprised the role in Spider-Man: No Way Home (2021), which is an MCU film.
Hiroyuki Sanada played Shingen Yashida in The Wolverine (2013) and Akihiko (Yakuza boss executed by Hawkeye) in Avengers: Endgame (2019). Archive footage of Hiroyuki Sanada from Avengers: Endgame was used in Hawkeye (2021) S01E01 "Never Meet Your Heroes".
Elena Satine played Lorelei in Agents of S.H.I.E.L.D. (2013) and then Sonya Simonson / Dreamer in The Gifted (2017).
Aaron Taylor-Johnson played Pietro Maximoff / Quicksilver in Captain America: The Winter Soldier (2014) and Avengers: Age of Ultron (2015). He will play Sergei Kravinoff / Kraven the Hunter in Kraven the Hunter (2023).
Jamie Foxx played Max Dillon / Electro in The Amazing Spider-Man 2 (2014), and reprised the role in Spider-Man: No Way Home (2021), which is an MCU film.
Evan Peters played Peter Maximoff / Quicksilver in X-Men: Days of Future Past (2014), X-Men: Apocalypse (2016), Deadpool 2 (2018), and Dark Phoenix (2019). He also played Ralph Bohner / "Pietro Maximoff" in WandaVision (2021), an MCU TV series.
Josh Brolin played Thanos in Guardians of the Galaxy (2014) and reprised these roles in subsequent MCU works featuring the character. He also played Nathan Summers/Cable in Deadpool 2 (2018).
Michael B. Jordan played Johnny Storm / Human Torch in Fantastic Four (2015), and then played Erik Stevens / N'Jadaka / Killlmonger in Black Panther (2018).
Donald Glover voiced Miles Morales / Spider-Man in Season 3 of the Ultimate Spider-Man animated TV series. He played Aaron Davis / Prowler in Spider-Man: Homecoming (2017). He had a cameo appearance as a variant of Prowler in Spider-Man: Across the Spider-Verse (2023).
Hayley Lovitt played a young Janet van Dyne / The Wasp in Ant-Man (2015) and Ant-Man and the Wasp (2018). She also played Sage in The Gifted (2017).
Brianna Hildebrand played Ellie Phimister/Negasonic Teenage Warhead in Deadpool (2016) and Deadpool 2 (2018) and will reprise the role in Deadpool 3, which is an MCU film.
Karan Soni played Dopinder in Deadpool (2016) and Deadpool 2 (2018). He voiced Pavitr Prabhakar / Spider-Man India in Spider-Man: Across the Spider-Verse (2023). He will reprise the role of Dopinder in Deadpool 3, which is an MCU film.
Leslie Uggams played Blind Al in Deadpool (2016) and Deadpool 2 (2018) and will reprise the role in Deadpool 3, which is an MCU film.
Shioli Kutsuna played Yukio in Deadpool 2 (2018) and will reprise the role in Deadpool 3, which is an MCU film.
Oscar Isaac played Apocalypse in X-Men: Apocalypse (2016), Marc Spector / Steven Grant / Jake Lockley / Moon Knight in Moon Knight (2022), and voiced Miguel O'Hara / Spider-Man 2099 in Spider-Man: Across the Spider-Verse (2023).
Mahershala Ali played Cornell Stokes / Cottonmouth in Marvel's Luke Cage (2016) on Netflix. He voiced Aaron Davis / Prowler in Spider-Man: Into the Spider-Verse (2018). He made a voice cameo as Blade in Eternals (2021). He is set to play Blade in a 2024 Blade film.
Daniel Kaluuya played W'Kabi in Black Panther (2018) and voiced Hobart "Hobie" Brown / Spider-Punk in Spider-Man: Across the Spider-Verse (2023).
Kathryn Hahn voiced Olivia Octavius / Doctor Octopus in Spider-Man: Into the Spider-Verse (2018) and then played Agatha Harkness / Agnes in WandaVision (2021). She will reprise her role as Agatha Harkness in the upcoming TV series, Agatha: Coven of Chaos (2023 or 2024).
Hailee Steinfeld voiced Gwen Stacy / Spider-Woman / Spider-Gwen in Spider-Man: Into the Spider-Verse (2018) and then played Kate Bishop in Hawkeye (2021). She reprised her role as Gwen Stacy / Spider-Woman in Spider-Man: Across the Spider-Verse (2023).
Lake Bell voiced Vanessa Fisk in Spider-Man: Into the Spider-Verse (2018), Natasha Romanoff / Black Widow in Season 1 of What If...? (2021 MCU TV series), and then played Dr. Graham in Black Panther: Wakanda Forever (2022).
Russell Crowe played Zeus in Thor: Love and Thunder (2022), and will play the father of Sergei Kravinoff / Kraven the Hunter in Kraven the Hunter (2023).
Note: To keep the list short, I am only including actors who have played live-action Marvel characters. This excludes voice actors who have voiced multiple Marvel characters but have not played any in live-action.