The big reason is the pacing. Okami splits pretty cleanly into three chapters divided by main regions: East Nippon, West Nippon, and Kamui.
In East Nippon, there are three major bosses: Spider Queen, Crimson Helm, and Orochi. Each presides pretty neatly over a segment of the plot and a themed dungeon, and it all ties together reasonably well.
In West Nippon, there are two major bosses: Blight and Nine-Tails. Nine-Tails also fights you in two miniboss fights, and the bossless Sunken Ship is arguably the game's most impressive dungeon aesthetically.
Then comes Kamui. Kamui has, in order: a trip to the past with a recycled major boss (True Orochi), a new major boss who nonetheless provides no significant new elements in the combat (the previous major bosses each have some factor that makes them unlike any enemy you've fought to that point, while the owl guys have a watered-down version of Nine-Tails' gimmick), that boss again accompanied by his twin brother, and then the Ark of Yamato, where you get to fight Spider Queen, Crimson Helm, Orochi, Blight, and Nine-Tails again before facing the final boss. Who is, I will concede, an impressive fight, but aesthetically jarring compared to anything else in the game.
And then Amaterasu sets sail for the Moon and the Celestial Plain, where we're told business will be taken care of. And the game is over.
I am pretty certain that originally, the final section of the game was to have been the Moon: following some business in the Ark of Yamato, the third arc of the game would have been concluded by blasting off to track down and deal with the source of the evils that had stowed away on board. The zone would likely have been populated with the enemies from the trip to the past; you know, the ones based on Japanese OOPAs who pop up in a one-time area and then never show again, almost as if the designers had built them before they had a place to put them? Most likely Kaguya would have re-entered the plot, making the diversion from the Sei-An plot to go do her sidequest a little less seemingly random and inexplicable. Presumably we would have had time to acclimate to an alien/technological aesthetic based on the aforementioned OOPAs, so it wouldn't seem so jarring after 30-50 hours of Japanese brushwork when the source of all darkness is a giant fetus inside a shapechanging robo-sphere armed with missiles and lasers.
And presumably, the ultimate weapon in the bead line would be earned from a boss fight or plot event like the other ultimate weapons instead of simply appearing unannounced in the weapon merchant's inventory in Sei-An City. And maybe the upgraded technique for ice would actually be earned like the other upgraded techniques instead of being an easter egg for anyone who thinks to paint an asterisk onscreen after earning the main ice technique.
That's all I've got right at this moment. I dunno, it seems like a lot to me.