Personally, I'd definitely lean 28mm over 15mm for this particular genre, if for no other reason than that I don't find Japanese historical or fantasy miniatures to be particularly well-represented in 15mm. I especially like both the Perry and Fenryll unarmored Samurai as potential Samurai Jack models.
In terms of rules, I think that Samurai Jack lends itself better to roleplaying than to miniature gaming, personally, but if interested in playing it as miniatures then I think my first stop would be Pulp Alley. I'd have the "Hero" player (be it Samurai Jack, the Scotsman, or some other hero invented for that world) played as a league with the Duo special rule, so only two very powerful models, against Aku's minions using the mastermind rule - so no leader on the table but lots of henchmen. I think that this would replicate the asymetric match-ups pretty well, and allows for all sorts of the sci-fi nonsense that you see in Samurai Jack. Supporting friendlies, like the explorer dogs from the pilot, could be plot points.
If playing a campaign, then in the final scenario you could change up the bad guys' league to no longer be a bunch of minions, but instead include some manifestation of Aku, maybe using the monster rules which are in one of the supplements. I also have to say, for a Samurai Jack campaign, Perilous Isle is a must-have. It starts you out in a city (could be considered Edo Japan, or whatever familiar past you like) and leads the heroes to a dangerous foreign land (in Samurai Jack's case, the future) where they encounter all kinds of monsters. I think this could be ideal for tabeltop-gaming Samurai Jack, and definitely worth looking into...