They set up that kind of tension in Fable III. You begin the game with your lover and eventually as events transpire you become separated (with them presuming you dead). When you finally reunite, they are in a relationship with this noble and virtuous person and you can basically take the high road and let them go or break up this relationship. It was a very interesting dynamic to have present, and it doesn't even begin to factor in that you could have very well formed a relationship with someone else yourself.
So, I think we might see that in Fallout 4. In fact, I would go so far as to say that your spouse will definitely survive and be in the Wasteland. You will find them at some point and have the opportunity to reunite with them and we might see any of the tensions I described above transpiring. I do not believe our spouse will die mainly because it strikes me as too contrived. Depending on the flow of the opening moments of the game, we are introduced to our family and then all hell breaks loose and we subsequently lose it all. It doesn't really seem to give enough time to develop any emotional connection or gravity, which is something I thought Fallout 3 did pretty decently when taking you through your life in the vault. "Growing" up beside your dad and experiencing some key moments helped to make his sudden departure sting, or at least it did for me. I mean I didn't feel a true emotional response, but it was easier to care about the events.
Now it is hard to make statements because we don't know the opening series of events. I'm betting money that finding our family or discovering their fate is going to factor into this somehow. I really think it would be an egregious error on the part of Bethesda to just wipe out our family at the beginning. Even for a game as dark tonally as Fallout 4, it seems like too much of a heavy hand that early. In a weird way, it would be like they didn't even matter, because by the time we get into the game good and proper, the interaction we had with our family will be a faint point in our minds and we will play like it never was a part of our history. In which case, it makes me wonder why give that background to begin with? There is no motivation and I think that is one of the big roles the family is going to play. They will be our primary motivation to do what we do. Now, depending on how things play out, I believe one of two things is going to happen. We will have a cathartic reunion with our family and in the course of finding them we will be exposed to several factions, groups, etc. and we will garner further motivation for completing events (making a safe home for our family, improving the wasteland, securing food/water/shelter, etc.) or, we will have them for a time and then lose them to some primary antagonist, which will then set up a classic revenge tale that will drive the rest of the narrative.
I would place a cool 50 bucks that this is exactly what is going to happen to get the ball rolling.