Ponyo was told by her father that she can't work magic and stay human. Remember that when she casts spells, she takes on that weird appearance that looks like a tadpole or a chicken. Or a vaguely anthropomorphic Tiktaalik.
Of course Fujimoto is so protective of the sea. He's literally married to her.
On that note, it could be argued that the union between Fujimoto and Granmamare represents the ocean as a whole. She's the goddess of mercy that recedes the floodwaters and guards life. He's the bitter, destructive side of the ocean that indirectly causes the flood in the first place. But because they're two halves of the same whole, they remain united and in love despite their differences.
Fujimoto sees humanity as evil for its destructive tendencies, in particular toward the ocean, and has been working to create a pool of elixer sufficient to cause a bust of ocean life that presumably would result in the end of humanity. Of course he feels that way, he's over two thousand years old meaning he got to see the change from simple sail boats that cause relatively little pollution to the most wasteful time in human history. It would have been heart breaking to watch the mix of pollution, overfishing, and a seeming ignorance to the state of the ocean. He just happened to snap right as we were starting to get the message on our own and clean up our mess.
If one looks closely at some background objects in Fujimoto's study, it becomes apparent that he is nearly two-thousand years old. However, Ponyo seems to be about five, and her sisters even younger. This means it's actually highly unlikely that he has no understanding of humans and their ways, and Fujimoto very well could have been only pretending to be a silly and overly-stressed anti-villain, and really did intend to wipe out humanity (and, impliedly, all life on land) using that potion Ponyo accidentally spilled while trying to make herself human. If this is true and his silliness was a facade to protect the innocence of his children, than we can safely assume Fujimoto has killed people in the past—knowing he's had centuries to do so and seems to have no qualms traumatizing *human* children trying to wreak havoc on humanity, he could actually have a very high body count.
He mentions that he was human once—which would have been centuries ago, long before environmental destruction became even close to half as severe as it is nowadays. What does this imply about Fujimoto's backstory? What could he have lived through that made him so hateful as to become inhuman from it and make it his life's work to destroy humanity in its entirety?
random but related to his age, he still uses Bernhilde as a name which was last popular around the 13th century.