Is Skyfall preparing the ground to some major change in the franchise?

Not at all, rather on the contrary.

They rather reintroduced classic characters, but adapted them to the new modern rebooted Bond, like Q (who is now rather a hacker than an inventor) or Moneypenny (who is much stronger and more self-confident than the languishing little secretary she was before the reboot). In the end Bond is a different character himself (and not just another actor), as introduced no later than Casino Royale.

It is true that the modern Bond is much more vulnerable (both physically and emotionally) and the stories center much more around Bond himself and his development. But those "major changes" rather started with Casino Royale and Skyfall is more of a step towards classic Bond movies (while still retaining the modernizations of the "Craig-era").

And I didn't find any hint that there could be a final episode. Bond had his difficulties in this movie (see this related question), but at the end he's more confident and ready to go on than ever before (and this related question). And in the end there will never be a final episode. If you cannot continue a storyline in a reasonable way, you just do a reboot (which is especially common nowadays).

What you may experience is, that the story of the movie centered much more around the internals of MI6 and directly involved major characters in dramatic events, especially M dying. This indeed somehow new ground may spark the deduction that if M can just die throughout the movie, then why not Bond also? But in fact the final scene somehow shows (and Mrs. Dench may forgive me for saying that) how replaceable M actually is and that it requires a bit more than his/her death to endanger the further continuation and overall immutability of James Bond's adventures. It is just that the new Craig-movies have a much closer relation to each other and a higher overall story-consistency. Or call it a more dynamic cross-movie development of the story and characters, compared to the rather ground-up start of virtually each of the pre-Craig movies (in fact Bond's wife and her death is the only major cross-movie story development of the pre-Craig era, I think). But this fine-grained development doesn't neccessarily need to imply major changes in the overall franchise (and in Skyfall it certainly didn't).

And like said, the emphasis on Bond's own character and development and his physical and emotional weakness are not a novum of Skyfall but rather of the modern Craig-Bond at a whole, it's just emphasized a bit more in this movie. But neither does it give me the impression of discovering totally new ground compared to the previous movies. It even promises more traditional directions, even if not dropping all the modernizations, in the future (personal disclaimer: I like both the "Craigian" modernizations as well as the more "traditional" Bond-movies).

And last but not least, I just found this related article which may provide some additional thoughts about Skyfall making a statement for retraditionalizing the franchise. Although I for myself wouldn't go that far, it provides some interresting views.