This sounds like a wonderful product, but I can't think of a system I'd play but would want to play less for this game than 5E. It sounds like the binary skill system of D&D without even something like skill challenges. I'm definitely not trying to yuck anyone's yum, but playing this with a system like Daggerheart or Grimwild (just to get started) would seem to go together like peas and carrots. And thoughts on how they deal with the mechanics side of things?
One of the things to understand about this setting is that it's not trying to recreate a Ghibli movie exactly. It has little interest in presenting deep crunch to dramatically change D&D's core loop. It wants to be Ghibli-flavored D&D, and it leans into that. This is not a disappointing compromise (unless you don't really want to play D&D), but rather simply a design decision that they execute on fairly well.
So, your protagonists are not (necessarily) Ghibli protagonists. They're still D&D protagonists. You won't be a five year old schoolboy who falls in love with a fish or a tween girl who works at a bathhouse or a schoolteacher with a sick wife. I mean, those are all fine bits of inspiration and backstory, but then you layer the D&D protagonist stuff on top and maybe your Obojima version of Satsuki from
Totoro is a young witch who is looking for her long-lost sister who disappeared into the fey realms when they were children. And your Obojima version of Sosuke from
Ponyo is a boy who fell in love with a fish and now is a young adult who swore the Oath of the River to always protect her, and now faces the ocean itself to prove his love is true. Your Obojima version of Chihiro from Spirited Away might need to kick some butt as a fey-pact warlock who made a deal with river spirits in order to escape the clutches of Yubaba (who might cast
fireball in this translation)
This does compromise the "fairy tale" element of some of the Ghibli stories. Because D&D isn't great at delivering on those vibes, and Obojima's intent is to be D&D, those vibes are left more to the realm of suggestion and theme than to mechanical expression. So, you're still a fantasy adventure protagonist, you're not a normal person accidentally caught up in supernatural events (except maybe as your back story).
Of course, Ghibli protagonists who are already in this vein, like Ashitaka, require a little less translation.
Obojima still tells stories revolving around dungeons (dangerous, life-threatening locations) and dragons (dangerous, life-threating creatures), and shows its influences in how naturalistic and relatable these antagonists are. There's a pretty extensive section detailing antagonist motivations and alternatives to simply slaying them that I think is very on-brand, though it is very much presented as "DM Advice" more than anything concrete. The individual characters that the designers add through the NPC's and monsters in the setting emphasize (a) dangerous natural and supernatural conditions and (b) individual characters whose intentions are likely to put them at cross-purposes to most people on Obojima. These antagonists mean that Obojima stories are often about feeling small in the face of the immense power of nature and magic, and about confronting adversaries who are less evil than they are misguided and insistent. What true evil there is tends to lurk in the otherworldly - corruption and fiends. The most powerful creatures on the island are over CR 20, but are also not really hostile, so you're only likely to fight them in some tragic circumstances, like the spreading corruption, or if one of the more relatable villains might need saving from their own nefarious actions.
It's also worth mentioning that in addition to Ghibli, another big influence is the Legend of Zelda (specifically a lot of Breath of the Wild vibes, including a frankly over-designed potion crafting section that is
fascinating, and very playable, but surprising for the amount of pages they spend on it!). So the peaceful village and quirky NPC's existing in the shadow of some great evil rising in the distance is a vibe the setting plays into as well. Deep, dark places can be haunted with undead and fiends. There are your "stock dangerous humanoids," the Howlers (think: less overtly fiendish gnolls). Dangerous wildlife. Very bread-and-butter D&D stuff. The design intent isn't to remove a plunge into a ruined tomb, it is just to give that delve a context and a vibe that is more full of whimsy than full of grimdark metal.
TL;DR: Obojima wants to be D&D. It's a particular style and flavor of D&D, but it isn't trying to be anything but D&D. It's quite successful at that, IMO.