The first two are AU but still vamp/slayer fics. They are also very long epics with multiple stories and the trouble in the marriage isn't immediate in either one. But when the trouble starts it is very very very good and realistic and heartbreaking all at once. But both have excellent spuffy endings.
The Baby Series by Mrs MuirSummary: Series of four epic fics covering the Babyverse. Spike is called away by Drusilla before he can meet Buffy at the Bronze in Tabula Rasa. He doesn't return to Sunnydale until after the fiasco of Xander and Anya's wedding. Things aren't the same as when he left town...especially Buffy.
Post-Series, Season 6, Season 7The Bittersweets Series By HerselfSummary: An ongoing series of Spike/Buffy tales, meant to be read in order. The first springs from "Wrecked" in season six; the series veers off from canon at that point.The second two stories are all human. The difficulty in the marriage are apparent pretty quickly and should fit your criteria quite well.
If I Lay Here by squawks I don't think this one is online any more – if you want a copy contact me through my contact here at TSR and I can send it to you.
Summary: A story about the trials and tribulations that might come with a relationship, and how sometimes difficult times can make the bond between people stronger. Quite angsty. Involves miscarriage. But there is most definitely a happy ending.
Sanctuary by MrsMuirSummary: William Nagle and Alexander Harris have been best friends since the first day they met at Hyperion Preparatory School. Through the years they have always been there for each other. But one of them holds a deadly secret that will affect William's future with Buffy, the woman he loves. Will Buffy be able to hold onto the man she loves or will the secret rip them apart?