The Elder Scrolls: It's the IX Divines, you milk-drinkers

[Calemyr]

Wait, what? A good reason for their friendship? If you go vampire side I could see it, but if you go Dawnguard side there's pretty much no reason at all for any friendship. By the end I can sort of see it, but (outside of alignment) there's no logical reason for the Dhovakiin to not leave Serana dead in Dimhollow and take the scroll back to Isran herself. Or if you decide you don't want to murder "innocent" vampires, I've yet to see any reason why you shouldn't let Isran deal with her at Ft. Dawnguard. The trip into the soul cairn is the only part of the DG quest chain would break, and I'm sure there would be some way to incorporate that w/o Serana if Bethesda had really wanted to. (And that would also avoid being forcibly saddled for hours of the game with someone who complains about the weather regardless of what it is and insists on zombifying nearly everything)

I only ever go the Dawnguard route. Vampire culture disgusts me, can't even stomach the Dark Brotherhood. Serana, however, is a different case. Your relationship with her evolves over an extended period of time and frankly is the strongest relationship in the game.

Spoiler: Dawnguard Spoilers

Show

When you first meet her, you're not certain what to make of her. She sure doesn't look like any vampire you've seen in the game before (even the recently fed ones are strikingly deformed). She doesn't attack you on sight, and she warns you that there are bigger dangers than her. She does nothing at all hostile against you, never threatening you at all. Even if you go straight to the Dawnguard, she doesn't leave in a huff or accuse you of treachery, she just hangs back while you discuss the situation with her superiors. If you treat her humanely, she is clearly grateful.

You take her home and flip her father the bird and that should be the end of it, right? No, when she assesses the situation she hunts you down again as the only person in the world she trusts enough to help her solve her mystery. You can't do it without her and she can't do it without you, and both of you need to see it done. You then go through a lengthy quest together where situations push her to expose far more of herself than she'd probably like. She introduces you to her mother and surprises everybody present (herself included) with the realization that you've done more for her in the short time you've been together than Valerica ever has. To her personal devastation, she admits that the one thing she wants above all - her family back - is the something she'll never get and quite possibly something she doesn't deserve.

Then you help her track down and sort out the source of the prophecy that destroyed her life and find out it's all a scam - a petty attempt at revenge by a priest whose god turned away from him when he turned (against his will) into a vampire. Then you go one step further. You end the against both Serana personally and the province of Skyrim in general - her father. You rally the Dawnguard, you storm the gates of home she'll never know as hers again, and you chase her father down to his sanctum and use the very weapon he's seeking to put him down once and for all. And what does Serana get for this? Acceptance. Acceptance from the Dawnguard itself. The very people that should hate her on principle have come to accept that she's more than a pair of fangs. And as for you? Well, she considers you her most treasured friend. She'll even abandon her vampirism for you, something she paid dearly to attain (Molag Bal doesn't get his title for nothing) whether it was her choice or not. When approached romantically (with an amulet of Mara) she at first says she's just not comfortable with shrines and religious places, but if pressed on the matter she admits she would like to but she believes she doesn't deserve that kind of happiness. And that guilt is the one thing you can't help her slay.

Compare that with the other allies you can get:
Lydia: You're my boss, as decreed by my Jarl.
Aela: Of course I'll marry you, you're the alpha wolf now.
Faendal: You removed my primary rival in courting this girl I like. You may have then stolen her for yourself, of course... Eh, I'll follow you into certain death anyway.
Cicero: The dear sweet mother says your the boss now, so of course I'll follow you.
Erik the Slayer: You talked my father into letting me become a mercenary, so I'll let you hire me.
Mjoll: You recovered the sword I lost, rekindling my desire for adventure, so sure, I'll do a complete 180 on my beliefs and follow you out there.

Everybody else you ally with in the game do so for one of two reasons: A) You did them a favor (usually a pretty petty one) or B) You outrank them. Very few of them have any meaningful reason at all for their connection to you, and even the ones that do don't earn it the way Serana does. The closest I can think of to people who can really have good, meaningful relationships to the Dragonborn are Idgrod Ravencrone and Balgruuf the Greater. Both of these Jarls take the deeds you do for them to heart and can put themselves at risk on one occasion or another at your request. Idgrod distracts the staff of the Thalmor Embassy for you (which is certain to bite her in the rear and she's smart enough to know that and do it anyway), while Balgruuf takes (what is probably) a complete unknown, brings you into his inner circle, and takes several risks on you well before you really prove yourself. (Which makes your potential betrayal sting all the more.)

So, yeah, I meant what I said. A good reason for their friendship. The most meaningful relationship in the game: born by accident, forged by necessity, and tempered by more give and take than is found anywhere else in the game. I won't play the game without her anymore. She's the only person in the game that seems to think of you as a person and not some blank-faced demigod, ironically just as you are the only person who can see her for more than a vampire.

^This. It annoys me so much every time I play the Dawnguard quest.

There is a reason, actually - Serana says herself that there are bigger threats in play than her, and working with her will help you fight them. You don't have to believe her, but there is absolutely a logical reason to let it play out and see where it leads, whether it's one you personally agree with or not. Even Isran (if you go talk to him before taking her home) says the chance of rooting out a hidden agenda (especially given the recent resurgence of organized vampires) is too important to pass up.

The simplest way to get past the 'must be a relative of Valerica to enter' part would be to take blood from Serana's corpse. Or, did anyone say it has to be an immediate relative's blood? Have a sidequest wherein Isran has you hunt down a book of Valerica's family tree and find a many-times-great-grand child of a niece of hers or something. Then persuade that person to give you some of their blood via Speech check/quest.

The Ideal Masters couldn't get through her defenses. The Ideal Masters. The only thing they could do was put up a barrier to seal her away and put an indentured dragon in charge of protecting it. Now, perhaps you could get through her defenses - you are the Dragonborn and that pretty much defines you as a massive Mary Sue - but I still think it wouldn't be a guarantee, especially after she discovers that you not only gutted a girl who did nothing to harm you but then bled her dry and carried around a vial of her blood for no reason at all.

Without Serana there is no Dawnguard quest line. You would have never found out about castle Volkihar (the Dawnguard didn't know of it*), you'd have never gotten into meet the madman in chief, you would have never learned about Valerica or her garden or the clearly non-traditional research she used to get into the Soul Cairn, you would have never gotten Valerica's Elder Scroll, and to cap it off, you would have never discovered there was a reason to do any of this in the first place - an Elder Scroll doesn't give you what you need to know, there's far too much in any one of them, you have to know what you're looking for before you turn to it.

* Which actually makes sense, if you think about it. The Vigilants of Stendarr are a reactionary force. Very few of them are proactive enough to even consider using research to look for trouble, they just go out and wander until they find something to kill, kill it, then go wandering for something else to kill. And the original Dawnguard, despite its reputation, had no interest in looking for vampires, it was only concerned with the one it was trying to secure. Isran has no intel either from the Vigilants or the fortress records that would tell him about Castle Volkihar. The only lead he has is Dimhollow, and Serana is the only source of information you find there. Killing her pretty much ends the Tyranny of the Sun prophecy before you even learn about it, at least until Harkon gets creative about things (and creativity does not come easily to that guy), but it doesn't remove Harkon from the game.