Certainly the World Government itself will be the last big villain of One Piece. Blackbeard may go down at Marinford (I think Luffy will fight Blackbeard at Marinford and win…wether or not it's a permanent victory remains to be seen of course as Blackbeard could show up again at Raftel). But certainly Raftel is not the end of One Piece. I think the final big chunk of the story only begins with Luffy reaching Raftel and becoming Pirate King.
As I've thought ever since chapter 100, when Dragon gave the quote from Roger that definitely seemed to be anti-WG, I've thought that Dragon had the same goal as Roger. All the information since about Roger and Dragon clearly shows Roger had big plans. First we found out Dragon was a revolutionary during Drum Island...a revolutionary who quotes the Pirate King? Wouldn't that mean the former King had the same goal as said revolutionary? Then we find out about Nico Robin, the Phoneglyphs, and the True History being hidden. We then find out Roger could read or had someone who could read those Phoneglyphs on his crew...he knew the True History...isn't it possible Dragon knows as well if he shares Roger's ideals? Next we see the extent to which the WG will go to hide that history in Enies Lobby, to use so many resources all to exterminate Nico Robin.
Finally, the two piece of the puzzle I was waiting for - Monkey D. Dragon and Gol D. Roger are both D's, sharing the same "inhereted strength of will." Robin and Rayleigh's conversation on Shabondy Archipelago really solidified this theory for me. Roger intentionally died and intentionally created the Great Pirate Era. He was a dying man, so he intentionally began the great era of piracy....but why? His successor, the next pirate king would need the same inherited strength of will, the Will of D. to reach Raftel. The True History remains hidden there as only the next Pirate King could use this information effectively. The World Government has shown itself to be a cruel and dominating force in the world of One Piece. They are the final villains, the ones Roger wanted to defeat, but could not due to his terminal illness. Rayleigh even said he woudl tell the Straw Hats the true history without hesitation on Shabondy if they wished to know....but truthfully they weren't ready.
Why wouldn't they be prepared if it's just a simple history lesson? Wouldn't this simple statement imply that the True History is so shocking it would cause a man like Luffy to want to act immediately? To go to war with the World Government directly before he's ready? I don't think it's a coincidenc that shortly after Luffy was unable to defeat Admiral Kizaru and Shichibukai Kuma. It showed just how weak he still is compared to the higher ups in the World Gov....and I somehow doubt the Shichibukai and Admirals are their top fighters. There's still Fleet Admiral Sengoku, and the Gourosei themselves, who bear the scars of warriors.
Who exactly will be the final opponents of the Straw Hat Pirates? I don't think they've been introduced yet. Who they will represent? Certainly, the World Government.