Anime that strives to be a little more universal in its approach either from the start or during the process of localization--Sanrio stuff, Dragonball, Ghibli, Pokemon--seems to be breaking through no problem.
Interestingly enough, anime is kind of similar in its home country. A lot of the stuff we discuss only airs in late-night TV slots, with individual series making money by selling only thousands (tens of thousands if they're lucky) of overpiced Blu-rays to a tiny group of hardcore fanatics. Meanwhile, mainstream shows like Dragonball get watched by tons of kids, and Ghibli movies top the box office.
But anyway, I think you're kind of right. There's absolutely a barrier to entry for anime and manga, and it's a tough ask to get people to overcome it. But it's not an insurmountable hurdle were a media company dedicated enough. I think the main issue is that rights-holders are reluctant to make that kind of push, because the returns are really uncertain, especially for companies more interested in their domestic market.
It took superheroes decades to make it into the American mainstream, and it didn't turn into the phenomenon it is today until a major media company saw enough of a pattern of scattered success in comic films to decide to buy a comic company and make a huge push. Efforts to sell anime and manga outside of their native format have more or less all been failures (like, say, the Dragonball Hollywood movie), and companies are still gun-shy after the crash of the US anime retail market in the mid 2000s.
There are some movie companies developing manga adaptations like Akira and Ghost in the Shell. If one of those succeeds, it could lead to more efforts. But someone has to plant that seed. There are absolutely issues with content in a lot of anime (you... really don't want to know more about Araragi's interest in Hachikuji), but if Hollywood could turn Wanted, a comic about villains ruling the world and raping and killing at their leisure, into a story about assassins protecting the world from the shadows, nothing is impossible.