Warning: contains spoilers for Avengers #55!
The villain and thanks to the events of Heroes Reborn, Mephisto and his many, many cronies know exactly what needs to be done. Avengers #55 reveals just how many Mephisto variants exist - and one of them points directly to an MCU incarnation.
During the events of the Heroes Reborn crossover story, the Earth was turned into a world without Avengers; the planet was instead protected by the Squadron Supreme. Only Blade ed the true reality, which was overwritten by Agent Coulson (now the President of the United States) using a hellish variation of the Cosmic Cube. The entire ordeal was revealed to be a pact between Coulson and Mephisto (hence the entire world worshipping him, and even "In Mephisto We Trust" printed on American currency), and the world was restored. But Mephisto never intended the Heroes Reborn world to last - it was merely a trial run.
In Avengers #55, Mephisto reappears through a portal, watching the Avengers in a direct callback to the end of Zack Snyder's Justice League. Mephisto warns Earth's Mightiest Heroes that he will soon return for the 616 universe, and he won't be alone. A two-page spread of Mephisto variants is shown that includes versions from every conceivable reality, including giants, dragons, monsters, and even a few pirates. But the most notable inclusion is a small, humanoid duck-shaped devil that bears a striking resemblance to Howard the Duck.
In these two pages, Marvel establishes that Mephisto exists in every conceivable reality, and in every conceivable form - including a duck-devil from Duckworld. Duckworld and the character Howard the Duck are far, far better known from the disastrous Howard the Duck film than any comic. Following that logic, a MCU variant of Mephisto isn't far behind; if the Prince of Darkness can take the form of a talking duck, surely he can appear in a film.
The Avengers are about to face their toughest opponents yet. Just one Mephisto can easily defeat all the Avengers (and has done so in the past), but thousands of them would be nigh-unstoppable. Short of a miracle, Mephisto and his variants will easily defeat anything or anyone that stands in their way.
