Theres been a pattern for this, during the 4th generation, Final Fantasy was a success in Japan but really only Japan. Then with the fifth generation FFVII's sales exploded and sold 10 million and the franchise became huge, the series is the second best selling PS1 franchise behind Crash Bandicoot (however there were several collections that came later which there are no sales of here so its possibly first).
Meanwhile in the fifth generation there was Grand Theft Auto 1 & 2 which sold 2.32 and 3.42, decent sales but there were over a couple dozen games thats sold better on PS1. With the sixth generation GTA really blew up, 11 million, 14 million, 18 million they just kept getting bigger it was by far the biggest franchise of the generation.
And meanwhile you had Call of Duty which its best selling game on PS2 was 2.8 million far behind Medal of Honor. But look at it this generation its easily surpassed GTAs peak and its the biggest franchise on both Xbox and PS3 and one of the biggest entertainment franchises in the world.
So what will be the break out hit with PS4 and Xbox 3? itd be something you really wouldnt expect, if you were told Call of Duty would outsell GTA 5 years ago youd never believe it, itd be something thats mildy successful now that does well but theres not all that much attention for it and its sales arnt setting the world on fire.
i couldnt really think of what it could be, however i think something that could become pretty big next generation is maybe the Red Dead series its sold very well and its gonna at least be nominated for GOTY so its not the same as FF, GTA, COD but thats the only thing i can see breaking out.