With Generation 5 being revealed as a distant sequel to Generation 4, rather than a complete reboot of the franchise, I think there's a natural expectation that there will be some references and nods to Friendship is Magic in the new series. We already know that the Mane Six will be historical figures thanks to promotional material regarding the upcoming film, but the timetable and state of Equestria indicated by the film's synopsis makes it seem evident that they will be long gone by the time our new group of protagonists trots onto the scene. However, it seems probable that some G4 characters will actually appear in G5, both to attract interest from G4 fans and for the simple fact that it's the same world, so why not? As such, I think it's worth considering just what legacy characters might appear in the new film or subsequent series.
- Dragons
Dragons have the advantage of being established as an incredibly long-lived race within the world of Equestria. Former Dragon Lord Torch was well over a thousand years old, having reached his adult size prior to the Pillars of Old Equestria joining together. Razer, the adult dragon introduced in Dragonshy, was similarly indicated to have a prodigious lifespan based on the fact that Twilight refers to his intended 100 year sleep in the episode as "a nap". It thus seems very likely that, unless the events of the new series take place insanely far into Equestria's future, that various dragon characters from Friendship is Magic could make return appearances.
Of the possible characters, there are three that seem like they have the greatest potential. Ember would certainly be an interesting case, particularly given the changes in Equestria's society and how it might affect their relationship with the Dragon Lands. Smolder is another intriguing case, though it might be a bit bittersweet to see her without most or all of her fellow Young Six. I suppose there's her brother, but Garble isn't exactly high on my list of characters I'd want to see in G5. Of course, easily the most significant G4 dragon who could return for G5 has to be our boy Spike. Of course, it might be a somewhat bittersweet inclusion at first, given that Spike will have not only outlived his pony friends and family, but have witnessed the decline of everything they worked to hard to build and preserve.
- Antagonists
The next group of characters who could potentially return for G5 are the various G4 antagonists who were neither killed nor reformed by the conclusion of the series. Of course, I'm not referring to the likes of Lightning Dust or Flim and Flam, whom I also expect will be long dead by the time of the new series. No, I'm thinking particularly of Queen Chrysalis, Lord Tirek, and Cozy Glow, who seem particularly likely to live into the future given that they were last seen encased in stone. Unless some comic following My Little Pony: Generations revisits the subject, I could see them remaining imprisoned until the time of Sunny Starscout and her friends. By that point, they could well be released by some new villain, a misguided character, or as a consequence of some magical/cosmic event or other.
The bowling team of doom aren't the only unresolved antagonists I could see returning in G4 by some means. The real Grogar's fate has yet to be determined, and after all that setup in the last season of G4 it seems like a G5 appearance wouldn't be too much of a stretch. Another, though less likely, prospect, is the darkness that formerly composed one half of the Pony of Shadows. The same sort of scenario that might free Tirek and co. could easily see accommodate the escape of this evil from limbo, and an Equestria where the tribes have become divided seems likely to be ripe with ponies who might be willing to join with this malevolent entity.
- Ponies
So far as the series has indicated, ponies seem to live a lifespan comparable to humans, though admittedly the vagueness of the timeline makes this somewhat difficult to determine. In any event, their lives are certainly finite, and if the Mane Six are only historical figures by the time of G5 I think it's safe to say that all other Earth ponies, Unicorns, and Pegasi we're familiar with in the series will also have passed, if they hadn't already by the time of The Last Problem as was implied to be the case with Granny Smith and Goldie Delicious. This is of course barring some sort of situation like the Pillars ending up in limbo, or some other means whereby a "mortal" pony character could have their lifespan prolonged far beyond what would normally be expected-this is a fantasy series, after all.
Of course, there are some other, more unusual Pony varieties that may not be bound by the same rules. We saw so little of the Bat Ponies, Crystal Ponies, and Kirin that we really don't know whether they age in the same fashion as the three main tribes, though that would be my expectation. Of course, Alicorns are another matter, at least in the case of Celestia and Luna, though I also don't expect them to still be around by this point. The only Alicorn I have any real expectation of being around, barring an entirely new character, is Flurry Heart, but even that could be a stretch.
- Animals/Creatures
My assumption is that most animals within the series (meaning the ones that can talk) have a lifespan comparable to the three main pony tribes. As such, I don't expect that any buffalo or yaks that might appear in G5 will be the ones we've gotten to know in G4. Whether the same holds true for the likes of Capper, Captain Celaeno, or the Diamond Dogs is unclear. It seems like Reindeer could theoretically be longer lived given their magical abilities, though I doubt anyone would be particularly excited to see a trio of one-off characters again.
It seems more likely that there might be some longer-lived species among the various fantastical creatures that share the world of Equestria with our pony friends. Changelings, Griffons, Hippogriffs, and other such beings could very well live longer than ponies. As such, it's possible that the likes of Thorax, Ocellus, Gilda, Gallus, Princess Skystar, and Silverstream could still be around, though there's no way to be sure at this point. The most likely individual in this category to still be around by this point is our favorite master of chaos, Discord. Of course, one has to wonder how the poor guy's faring without his best friend Fluttershy to keep him company anymore...