|A break up lacks the emotional impact of Dean walking into the house and finding her dead. Besides it's a family tradition (John went through losing Mary, Sam lost Jess, it's Dean's turn) and is in keeping with the whole recalling season one. I mean how much impact would the first episode had if Sam came home and Jessica had left him so he decides that without her he might as well hunt? Zero compaired to her ending up flambe on the cealing of their place. This will give Dean a personal motive to get back into the game. For years he did it for his mom and becasue of his dad NOW it's REALLY personal.|
Jess' death in Season 1 worked because at that time Sam was young, over his Mom's death (he wasn't gravely affected by it, hence that mini-fight with Dean on the bridge in Ep1), and never for a moment expected anything like that to happen to him. It was an event that knocked out the very foundation of the picture-perfect life he'd built for himself.
Their mother's death had a similar reaction on John because he wasn't a hunter and didn't know WTF happened with Mary on the ceiling and the 'guy' in the room, their life and family completely devastated out of the blue. That propelled him into near-insanity while seeking for answers.
Will Lisa's death have the same impact on Dean - who has lost EVERYONE he's ever cared for in his life (with the meager exception of Bobby?) He's lost his father, mother, brother, countless friends, been through the apocalypse, and is now jaded into nothingness.
So I really doubt Dean needs a 'personal motive' to get back into the game. Something like Lisa dying and thus throwing him back out there will be the easy way out, because then he becomes the 'victim', and the game becomes about revenge, and we do S1 all over again, only this time with Dean moping instead of Sam.
A much more plausible event would be that some event puts him in contact with Sam, and he makes the CONSCIOUS decision to LEAVE Lisa + kid - either to protect them and / or to follow his new mission. Unlike say, a Jess-Sam college-kids breakup, THIS will have impact, because it will burden Dean with guilt at having to make a choice again, leaving someone he consciously committed to (as a last option, but still), and will draw him unwillingly - yet not as a 'victim' per se - back into the scene.
All emotional disasters don't need explosions on the ceiling. If done properly, Dean being torn away from barely-stitched-together love and peace can be wrenching as hell, while allowing him to own some responsibility for choosing to return to the hunt.