There are a couple hanging plot threads from previous season which could factor into this and I think point to an intriguing possibility. The Doctor will refound the time lords.
1.) We know that without the time lords to regulate things, time has become much more mutable and the Doctor has been playing fast and loose with the rules. Despite the doctor being a renegade, I think he will see the value in having someone to "run away from" who will take on the more mundane tasks of guarding time while he does his heroic gallivanting.
2.) Jenny. Though her introductory episode wasn't the best, I have no ill will towards the character and wouldn't mind seeing her pop up again. Nor do I mind the doctor having a family of some sort. The very first doctor had a granddaughter and I see no reason to disbelieve that she was his actual biological relative. Jenny means there is another time lord out there and as I recall Moffatt was the one who didn't want her to be killed off, so now that he's the show-runner it seems likely he will include her in future stories like he did with River.
3.) Captain Jack was a member of a Time Agency which had similar responsibilities to the Time Lords and River appears to be from around the same era seeing as she has a squareness gun and can use the vortex manipulator. River may or may not be the Doctor's wife, but she may be his "comrade in arms"; someone he can level with and trust implicitly. Somewhere, somebody got the idea that the time stream needed protecting and, with the original Time Lords out of the picture, someone more humble, such as the humans, had to step up and take their place.
4.) Omega is returning. As much as I dislike the trend of universe ending threats popping up in every finale since series 4, Omega is probably the most credible in terms of motive and ability. Where Rassilon just suddenly decided to destroy the universe to propel himself and the time lords to further glory, Omega has a history of being a mean SOB that resents the matter universe and the Doctor. Though the destruction of the Time Lords was necessary to protect the universe, the Doctor may have inadvertently left it open to attack from outside.
5.) The time agency may have inherited the responsibilities of the Time Lords, but not their competence. They will need the real McCoy, such as the Doctor and Jenny, as the pillars of the resistance against Omega.
The way I see it going is probably River and Jenny will show up in series 6, for the finale at least, and the finale is when the Doctor finally discovers Omega was behind the cracks. Then series 6b/series 7 will be him, River, Jenny, Amy and Rory, and possibly Captain Jack, either working with the Time Agency or actually founding it. Instead of a Gallifreyan only club, the new "Time Lords" will come from many races and operate on many scales to thwart different levels of threat, from local to cosmic.
Though it wouldn't be the same as miraculously bringing back the original Time Lords, it would end the "lonely God/Last of the Timelords" plot line introduced since the beginning of the new series, and yet not seem like a cop out because it is not creating an identical situation to the original series. That to me would justify the phrase "everything changes" because it would alter how Moffatt and any future show runners write stories and allow the Doctor to bend the rules a bit more since there's somebody around to smooth over the rough patches. There's also the potential for internecine strife within the Time Agency if someone wants to "fix" history "for the better", which may give River a motive for killing someone to protect the integrity of time.
- we really need a Cylon smiley. She can't kill the Doctor surley? I will be pissed if Smith leaves after only 2 seasons.
