Here are the best selling PS1 games:
http://www.vgchartz.com/games/index.php?&results=50&name=&console=PS&keyword=&publisher=&genre=&order=Sales&boxart=Both&showdeleted=®ion=All&alphasort=
The majority of them are exclusive, thanks to the dominance the PS1 enjoyed. I would post the PS2 link, but really there's nothing wildly exciting on there that doesn't already have an announced or released sequel, except maybe Jak. But I hope this isn't Jak, because Jak exists anyway.
We have several Final Fantasies on the list, but with FOUR FF games due for release in the next few years (two of them PS3 exclusive), that's nothing huge. Gran Turismo's sequel is coming this year, Crash Bandicoot (which was my guess) is there, along with its brother Spyro, which didn't sell as well, but was successful nonetheless, Tekken (wow Tekken 3 sold nearly 7 million!) has a sequel planned for this year, RE and MGS have had sequels this gen, same with Tomb Raider, Rayman has been destroyed by Ubisoft, and nothing else, except Syphon Filter, is really worth mentioning. Again, Syphon Filter is not huge. So it depends how loosely this site is using the term "huge".
There was one other series that appeared a couple of times- Driver. I've never heard of it, what is it? Is it huge? The sales suggest that it is. But, on checking Wikipedia, it's already announced multiplat.
Spyro and Crash look like the only two games it could really be. And with neither having seen a decent iteration since the PS1, it would be a massive leap over the (real) predecessor, but also familiar.
(Former) Lead Moderator and (Eternal) VGC Detective 
