Personally I kinda feel like people are starting to lose their imagination when they say "Oh you couldn't do this" or "That just wouldn't work", etc. I feel like you can do anything in a movie, even if it has a more real-world tone, it's still a fictional real world, where anything is possible. I think people underestimate the audience, and put unnecessary restraints on what people will and won't accept. I think if you do it with quality and care, people will buy into anything you sell them.
A Kirby inspired Galactus can be done. There are so many extremely talented and creative people out there, there's really no reason they couldn't bring that to life if they actually put in the effort instead of being afraid and playing it safe.
MODOK. Yes, he's a ridiculous looking character in the comics, but I don't think that makes him impossible to do. You could easily do something really creepy with him, and you don't necessarily have to shy away from him looking ridiculous. Go ahead and let there be some humor about it. Marvel characters always take shots at MODOK's appearance in the comics, why not bring that attitude to the films as well. People will be okay with him looking weird if the film acknowledges it as well.
I think the only villains who wouldn't work aren't because of their looks, but because they're just quality characters to begin with. Hypno Hustler, Typeface, Gamecock, Leapfrog, THOSE are villains you couldn't make work, even if you made them look awesome they're just lame concepts.
