Let's stick to the concept of cheating rather than that of breaking up. A fair few couples do cheat on each other, but don't quite break up simply because of it. Turns out emotional attachments are much too strong to completely break with a simple physical act such as having sex. Damage, yes...but not break.
First of all, it's important to distinguish the fact that cheating is primarily a matter of breaking your partner's trust in you through promiscuity. Swinger couples, for example, have sex with many other people, but it's okay - because they trust each other to keep love and sex seperate. So for me the question of who would cheat on who in all of the 5 possible pairings moreso falls down to this: Who would be the most or the least trustworthy when it comes to sex?
And honestly, in any pairing, one cannot ignore just how susceptible Hisao would be to cheating. Quite possibly well above most of the girls and not just because he's a filthy man and all men think with their dicks all the time, but because his life expectancy is at 30 years of age, give or take a few depending on which arc we're talking about (Emi's for the longest lifespan, Lilly's for the shortest in my opinion). With that kind of factor constantly in the back of a man's mind, one tends to always think of all the things they haven't done yet...and yeah, having sex with someone other than your first love would kind of fall under that category. This is not to say that Hisao would always be the cheater...but it is to say that, under normal circumstances, a man of his age would be far more under threat of it than any of the girls if he had that kind of Damocles' sword hanging over him all the time.
As for the girls, well, it depends on what kinds of personality they would have, wouldn't it? Since the 3 years rule is in place we can safely assume that the events of the good endings transpired, so we can extrapolate from that:
Honestly, her personality doesn't change that much with her good ending. She still likes to get hooked on pleasurable activity (like tea or having a romp when the mood strikes her), still tends to dodge or avoid thinking too hard on her own decisions (or lack thereof), that contributed to Hisao winding up with heart attacks, and this makes her a bit moreso susceptible to cheating than most would dare admit. Because she rarely thinks on how she herself could change things about herself and rather thinks on how she could merely cope and tolerate the way things are - something that never works out in the long run when it comes to personal decisions. Coupled with Hisao having the shortest lifespan as well and...yeah, I forsee trouble here. Still, given how Hisao comes across during his talks with Akira, I'd say Lilly'd be the first to cheat with Hisao feeling validated by it and following her lead soon after (which wouldn't make it any better really). Damn, I know I'm gonna get flak for this one.
Some potential exists here for cheating, I think. But given the fact that Shizune does change in the good ending towards a person that does manage to learn from others (Misha) and who actually sets a goal for herself, I'd honestly say she's not that much under threat of committing it. Add to that the fact that she will probably remain the workaholic she is as well as how her intelligence guides her moreso than her emotions and yeah, I definitely see little reason for her to break that trust. That being said, her relationship with Hisao would also be pretty loose. He'd work to apply and stay in Yamaku as a teacher while she'd go off on her quest to become a philanthropist so they'd probably not see much of each other - which does tend to increase the odds of one party or the other cheating. But oddly enough...I don't think either of them would do it in the end, because of how cerebral both of them are. So no, I don't think it'd happen here.
A lot of things change with Hanako with her good ending. She might not quite have the confidence she wants to have yet, but she is well on her way and after 3 years time yeah...I think she'd be fine in that respect. Add to that that it was Hisao who was directly responsible for her gaining it and I think she'd be fiercely loyal to him so - next to no chance whatsoever of her cheating on him. Would Hisao do it? Well...in her arc it is established that Hisao was, in fact, wounded moreso than he cared to admit to himself with his heart attack and leaving his former life behind. So much so that it led him to being afraid of losing Hanako, which in the end brought the two together on the same level. Would he change in 3 years time as she did or would he not?
What Hanako did for Hisao was make him moreso honest with just how fragile he really was, so if another girl came along and spoke honestly to who Hisao was 3 years later...yeah, he could become enamored with her too. So I'd say there is a chance of Hisao cheating on Hanako, but even if it happened it would've been due to him actually having feelings for that other person rather than just your casual romp. So yeah...there is a chance, but it's a slight one from Hisao's end.
Well, let's see, shall we? Honestly, if we were talking about Emi from the bad ending I would say - hell yes, she would cheat because it'd be the perfect way to mask her true intent: trying to push Hisao away before she could get too emotionally attached to him. In fact, in hindsight, I'm surprised that her bad ending doesn't conclude with Hisao waiting longer than that 1 week to speak with her and next time him seeing Emi with another boy as she says to him something like: "You weren't the first and sure as heck don't have to be the last." with a shrug. That'd probably drive the soul-crushing point of it all even better.
But since it is necessarily Emi from the good ending, and after 3 years, the equation changes. She risked emotional investment into Hisao, the likes of which she had never dared to ever since her accident - that's not something that you break off all that lightly. Would she feel the temptation of a quick romp with someone that caught her fancy? Sure - she's very extroverted, has a very relaxed attitued towards sex and it'd no doubt always be there. But even if she did, it would not be something that would last for very long and she would always come back to Hisao. That is...if he wanted her back. On Hisao's end I honestly don't see it happening. He primarily decides with his brains in Emi's arc and is pretty much the most standup guy of all the arcs. So in the end I'd say, yeah...there is a chance, but it's a slight one from Emi's end.
Honestly this one is the hardest to predict out of them all. In Emi's arc it is specifically noted that Rin doesn't quite 'get' the difference between boyfriends/girlfriends and just regular friends all that well. In that respect, she has trouble noting the whole 'trust' factor that usually comes with those designations. But again...we're not talking about that Rin, we're talking about the one from the good ending. And she does change a fair bit, it's just not immediately visible or apparent. With the good ending Hisao shows Rin that, in his own words, she doesn't have to be alone, so long as there is a person to whom she can come back to from under the rain. Rin takes this in stride and by the end she also notes that Hisao has been a kind person to her, even when he really wasn't.
So does this make her attached to him? Not quite. If someone like Hisao were to come along in Rin's life, I honestly don't think she'd perceive it as that bad to 'get together' with that person the same way as she did with Hisao. The chances of it happening would be astronomical (heck, Hisao and Rin getting together is in itself something that I consider almost impossible to actually happen IRL), but she would certainly feel few inhibitions towards it simply because 'Why not?' Out of all the girls, she'd probably be the most suitable for a swinger lifestyle, even if she doesn't have that strong of a sex drive.
So it's a bit of a shame that Hisao isn't like that himself, because he is very much so attached to her. After all, she was the person who got him out of his cynical frame of mind, who showed him all the different ways to get on with life without having it feel like a burden. In fact I'd say he's about as fiercely devoted to Rin as Hanako is to Hisao and that...could easily turn out to be a problem because I don't think Rin thinks of him that way. Still after 3 years time...who knows how Rin might turn out after living with him. But if I were to go purely on the good ending, I'd say yes - there is a real chance of cheating from the side of Rin, even if it's highly unlikely to happen due to not many people in the world being able to connect with her as Hisao did and even though she would honestly never quite understand the concept of cheating and how it could hurt Hisao.