My MU would be something like that:
There are no abstract cosmic entities like Eternity, Death, Chaos, Order, etc. Galactus is the top, and no one else is in his league.
Alternate realities can't collide to the main one, and alternate reality characters can never stay for good in the main one (let's call it 666
Metahumans are usually popular when public and government controlled, but still provoke diverse reactions. Not anywhere near mutants, though.
The Avengers are under control of the UN. They are supposed to represent the world, therefore the team would not be dominated by Americans. It would be something like that: Captain America representing U.S. (obviously), Black Widow for Russia, Sunfire as Japan (he would not be a mutant) representative, Black Panther for Wakanda, Captain Britain for UK, Storm for Kenya (she has born there, and is the sole mutant representative), Thor (which would be exactly like Ultimate Thor, except for no weather powers, since Storm is already here) for Norway, and Hercules for Greece. The misrepresentation of the 3rd world countries would be noticed.
The FF is employed by the government. The government uses heavily the fact that they are a family, and they are supposed to represent the American dream and way of life. In some measure, of all them, but specially Johnny, have problems in having to play this perfect little family role instead of being themselves.
The Ultimates would be a private team created and funded by Tony Stark, based on the West Coast. It would have Iron Man, Wasp, Henry Pym, She-Hulk, Hawkeye, Falcon, Ms. Marvel and Wonder Man. It would be more popular in the West than in the East of the US (not surprisingly) and politicians and the public in general would be divided in whether the team should be allowed to exist or not, to be government sponsored or disbanded.
Mutants would be feared and hated, etc, but it would be played upon a lot more the mutant baby boom, and the fact that many have deformed appearances. I would say there are only, let's say, 10 million mutants, most with weird looks and not very powerful, but it's number increases every day, and with time they will born even more powerful.
You would have two X-men teams: the public relations one, based on the mansion, with Cyclops, Jean (no Phoenix Force), Emma, Iceman (out of the closet from the start), Colossus, Polaris, Havok and Kitty, all pretty and worried about playing nice to the public, and another one based on the Outback, with Nightcrawler, Beast, Darwin, Archangel (who would already begin with his Horsemen look and powers, which would be natural) Quicksilver, Scarlet Witch, Gambit and Rogue, which would be composed all of weird looking mutants (the first four i mentioned) or former criminals (the rest), the ones which Xavier would prefer to hide. The conflict between the "A" and the "B" team, and the hypocritical behavior of Xavier in not exposing the other team would be approached several times, as well as the more violent conduct of the Outback team, which would have way less problems to kill.
Wolverine never joined any group, remembers everything, and has a healing factor in the 80's level, which would never increase it's capacity. And, of course, he would never fight the Sentry, the Hulk, etc. He could work both as a hero or as a mercenary, although he would never kill heroes or innocents. He would be much more of a loner than he already is, and would have few friends. His loneliness would be a major theme.
Both the Hulk and the Sentry are viewed by the general public as menaces and other heroes are pressured to capture or even kill them. At least the Sentry often disappears to space, so the Hulk is used as the prime example why metahumans should not be allowed.
Spider-Man is a hero which divides opinions. The kids adore him, but he's still viewed by many as more of a threat than anything else. J.J. would not have anything personal against him, but would make several anti-Spidey articles just because he makes money with them, both by selling more newspapers and by being financed by Wilson Fisk, and would end up becoming a worse enemy for Spidey than anyone else.
Matt Murdock is a anti-mutants lawyer that becomes Daredevil at night and fights crime. His real function would be to demoralize the anti-mutant crusade, although it could work against them quite often. And, yes, he would be a mutant.
The Silver Surfer would be the most powerful hero of the universe, but he would be much less powerful than he is on the 616. In vengeance for leave him, Galactus did consume his world, and now he wanders around the Universe trying to saving worlds and protecting life. He would also be trying to make worlds stronger so they could beat Galactus by making them fight him first and be prepared. Because of the damage he causes, he would be hated all around the Universe, even when he does make the planets strong enough, or when his activities have nothing to do with that, he's just fighting villains. He would be one of the most tragic heroes.
There would be much less "let's destroy the whole world/universe" villains, and more people like Kingpin, Sinister or the High Evolutionary, whose motivations and goals do not necessarily affect all mankind, and, because of that, have more chance of winning, since we all know that Apocalypse, Ultron, Galactus, etc, don't have a chance.