Could we see/hear of the death of a TNG crew member? If so, I'd guess Beverly. This could also allow Wesley to cameo in some fashion. This would certainly hurt Picard as they seemingly never did get married (and divorced) like the TNG finale suggested. He'd be full of regret with things left unsaid.
Then step in Q, probably with the guise of putting humanity on trial or some other machination, who will ultimately allow Picard to revisit the past and maybe along the way allow him to put things right, because deep down he wants to see him happy. Q is selfish and arrogant but he does seem to have a soft spot for the ent-d crew, particularly Picard.
If they're jumping around in the past we might even see a ds9 tribbles style episode where they're on the ent-d during the events of an older episode?!