Ponyo on the Cliff by the Sea/WMG

Fujimoto is Mako Tsunami.
He and the ocean have resolved their differences and got a ton of kids. Also, prolonged exposure to the sea reveals that Mako's hair is actually red.
 * Freaky fish kids, even.
 * Although he seems to have become an amphibian (judging from his ability to be in the air as long as he stays damp), which is really not fair. Freaky frog guy?

Ponyo's age is dictated by what she wants

 * Before she left the water she was the eldest daughter who was able to manage a ton of toddler fish on her own. This was prob. the only life she knew so she went with it, no reason to rebel. Upon meeting Sosuke and having licked his blood to kickstart her powers and motivation to leave, she begins to evolve. Back with her father she very much acts out the rebellious teen runaway. Again, capable. When she gets back to land, to Sosuke who is whats she wants she becomes like him. Physcially and mentally. This may explain why her parents were willing to let her leave. She'd either age with Sosuke, or she would grow to whatever was fitting.

Granmamare is Ariel when she becomes queen of the sea.
Well, it explains how accepting she is of her daughter wanting to be human.
 * And she moved to Japan?
 * All the way from Atlantica? And Fujimoto is her second husband?
 * The Little Mermaid was a long time ago, and We Are as Mayflies. Mermaids live at least three times longer than humans.

Fujimoto is Captain Nemo.
He was just hiding. Who would have guessed?
 * That's crazy. You're crazy.

He hates humans, he builds tons of cool steampunk technology, and he has vaults from the nineteenth and twentieth centuriesâ€¦

Fujimoto is a descendant of Howl and Sophie.
Their children lived in Japan and either intermarried or used Japanese names to fit in.

Lisa is The/a Stig.
Black and white outfit, Drives Like Crazy yet skillfully and thinks nothing of it, and finds an opposites-attract love with a guy who loves boats.

Lisa is Satsuki.
She seems to accept the whole "fish-turned-into-a-girl" thing quickly. Clearly she's had experience with cute supernatural occurrences. Plus there's a totoro on her fridge.
 * Also, the boy Satsuki becomes friends with grows up to be Souske's father. The hat Souske wears is the one he wore in "Totoro".
 * Backed up even more when she sings a little bit from the Totoro theme song (remember when Sosuke cheered her up and she went "happy as can be"/"watashi wa genki"?)

Lisa is a grown-up Kiki.

 * Nonsense, the senior citizen with the huge bow is a grown-up Kiki.

Fujimoto is an AU Taro Urashima.
Think about it. Both are/were humans who somehow lived underwater for a time, met a beautiful water spirit, and fell in love. The original Taro left to go home; Fujimoto stayed underwater and lived forever thanks to the Year Inside, Hour Outside.

Ponyo is actually Sosuke's new younger sister
Think about it. Heck, the last few scenes near the end (that involved an ovum-like vessel for Lisa and the seniors to breathe in, no less!) appeared to be a extremely subtle metaphor for a pregnency. The love between Ponyo and Sosuke can be easily taken as a platonic, sibling love as well. Why else would they include a scene where a new mother explains breast milk?
 * Additionally, the scene where Ponyo's sisters pop the bubble she was trapped in is very reminiscent of sperm fertilizing an egg.

The whole thing was a Batman Gambit on the part of Granmamare to have Ponyo become human
The Goddess knew that humanity and nature (via the sea) needed to come back together, and saw that Ponyo would be a way. So she stuck Ponyo and her sisters with her overprotective, but adorably Cloudcuckoolander husband, who would remain distracted by his "work" to give Ponyo the freedom to be curious and just rebellious enough to go off on her own. Ponyo started coming into her greatest power at the most curious and "innocent" time of life to be able to create a close bond with a human child. It was pretty much a given by that point. (Seriously, does anyone think Fujimoto really could have gotten away with getting rid of humanity and restarting life from the sea? He can't even fix a stuck door.)

Ponyo will grow up to be an oceanographer
During the test of love, Granmamare askes Sosuke if he could still love Ponyo if she walked in both worlds. If Granmamare intended her daughter to be a sort of ambassador of sea life, it makes sense that she'll become the Japanese answer to Jacques Cousteau.

Ponyo can use Spiral Energy
She willed herself to grow hands and feet and eventually become human, like Boota. Her magic seems to be directly tied to her willpower, though she's still to young to know how to use it effectively.

Lisa is actually Sousuke's stepmother, not mother
On a slightly more believable note than the above entries, Sousuke never actually calls Lisa 'mother'. He always calls her 'Lisa'. When Sousuke and Ponyo are on their toy boat and meet up with the couple with the baby, the father says that Sousuke is 'Lisa's boy'. In the original Japanese, he uses the word 'otoko', which literally means 'boy child', not 'musuko', which means 'son'. But Sousuke does refer to Kouichi as his father, leading to the belief that Lisa is actually Sousuke's stepmother.

Everything after Sousuke and Ponyo leave the house is a Secret Test of Character
Granmammare and Fujimoto set up a Batman Gambit to tire out Ponyo reverting her to "gold fish" form if Sousuke had abandoned Ponyo, say to look for his mother, then the disaster would have happened as well as Ponyo turning into sea foam. He didn't, so all they need is a verbal conformation that Sousuke accepted Ponyo the way she is/was/will-be.
 * Wasn't that canon?

Lisa is a grown-up Chihiro.
While she doesn't remember her experiences in Yubaba's bathhouse, she probably subconsciously retains a fair amount of it. That's the reason she's so quick to believe Sousuke's explanation about who Ponyo is- subconsciously she remembers that she's seen much stranger things before. Her love of Haku, a river spirit, changed into a general love of the water- hence the reason she married a sailor and lives so close to the sea.

Granmamare is Amphitrite and Fujimoto is Poseidon.Or...yeah.

 * Alternatively, Thalassa and Pontus. Thalassa being the sea itself, and both spawning fish.

Ponyo will continue to need blood in order to sustain her human form.
In Ponyo 2: Blood Is Thicker, Ponyo will accidentally unlock her magical powers and will once again find herself reverting into a fish. Shortly afterward, the Tomonoura police will discover Toki's completely exsanguinated corpse buried behind the Senior Center...
 * You Magnificent Bastard! I salute you!!
 * So she's some kind of fish Chiropteran?