I think Isaac's chances revolve completely around his role, if any, in the next GS game. Overall, I think its fairly certain that we will get a GS character, due to fan demand/the fact that it seems that Nintendo is treating it as a important series by letting it get into their press conference. The problem with Isaac though is that he was only the main character for one game, and just a major character in the second. If the third doesn't have him show up at all, I'd think that Sakurai would just go with the new protagonist, as it would be the most people would be familliar with at the time. If Isaac does come back to have a larger enough role in GS3 though, then I think he does stand a good chance of getting in. Of course, I can't help but think that SSB4's generation of clones may include both Isaac and the new protogonist. (Poor Felix...)
Golden Sun looks like it's turning into an evolving series like Pokemon, Fire Emblem, and EarthBound. I think it's best to compare Isaac to the main protagonists we got from those three:
Pokemon - Red/Ash; the original Trainer, also the most popular.
Fire Emblem - Marth; the original Lord, also the most popular.
EarthBound - Ness; the second hero, also the most popular.
All three characters were the most popular in their series (most popular Trainer in Red's case). Two of them were the originals, but Ness is not. Popularity takes priority over being first it seems.
Now if you suppose that Ness was included over Ninten because the two are so similar that they could be considered the same character, then it's just evidence that the first guy gets in over the newer ones. Ness would simply be the original and Ninten would only be a name. I doubt that though. Almost everyone sees them as seperate (if similar) characters.
You could say Ninten was considered before being disqualified by being JP only, but that assumes that Sakurai was more concerned about regional exclusivity than popularity (and since Europe never got Ness either, I doubt that's the case). That'd be some serious backwards logic though. Plus the whole "no evidence" thing.
Anyway, the Golden Sun DS guy shouldn't even warrant consideration unless he's as popular or more popular than Isaac. And that probably won't happen ever, let alone by SSB4.
Well that was pretty by-the-book. BTW is TMNT Smash Up worth renting? Or buying for that matter?
I hear it's worth renting at the very least. The online is supposed to be much more stable than Brawl but the game has a serious lack of Bebop and Rocksteady.