2012 was Jeb's year to win the nomination. I remember reading something in late 2015 that rang true to me: by that point most of the voters who put Jeb into the Florida governors mansion were dead, which was a huge handicap for him in terms of his ability to connect with the electorate. Beyond that the mood of the GOP electorate had drifted far away from establishment conservatism in a way that it hadn't four years earlier. If he was going to have any shot it wouldn't be in 2008 (which, to his credit, he realized) or in 2016 for the reasons I just stated. So that leaves 2012.
I don't think you need Romney to lose in 2008 to get Jeb Bush in 2012. It's hard to remember at this point in time, but in 2010-2011 the "establishment" wasn't sold on Romney. Folks like Haley Barbour were trying to find someone else to run as the establishment candidate; they were so hard up they considered running Governor Mitch Daniels of Indiana before he told them "no." I think that Jeb preempts Romney as the favorite of the beltway and donor crowds that year to the point that Romney likely wouldn't run. My money would be on him winning the nomination while facing some of the same challenges that Mitt's campaign did during the primaries. Ultimately, I think he'd lose the general to Obama because of the "Bush Fatigue."
As far as his VP nominee, that's a tougher question. Bush is a peevish guy who doesn't necessarily play well with others or let bygones be bygones, from what I understand, so that woudl rule out anyone who runs against him. He's wonkish and not a terribly charismatic guy, so I think that rules out Paul Ryan. Depending on how indebted he feels to Barbour, that might make a good selection. Someone like Huckabee wouldn't be the worst addition either, if they can get over their differences. Basically, he'll need to find someone who can fire up the base for him and bring some charisma to the ticket, but I'm not sure who that would be. Christie, maybe? I don't know.
If he loses that year, though, he's done. The Bushes will have spent the last of their dynastic and political capital for at least a generation, pretty much just like we're seeing today.