Not as hard as it sounds. True, Drusilla/Spike and Drusilla/Angel(us) defined Dru as a character in many senses. But in Angel season 2, so did Drusilla/Darla, with their shopping sprees and subtext/text attitude. She also shows a liking of Lilah (admiring her soft skin in Reunion and referring to her as "wicked" in Redefinition). So Dru-slash is not too far fetched. So, how it's done?
First of all, let's recap what the Jossverse has given us when it comes to Dru relationships: Spike, Angelus, Darla and to some extent both a chaos and a slime demon (Dru, what were you thinking, dear?). So, quoting Amberina, "she's willing to date demons, dating a woman isn't incredibly strange." It's all about the right circumstances for each woman.
In the beginning it's a matter of strength. Drusilla both fears and adores the powerful ones. She was sired by Angelus, the Scourge of Europe. Spike was his Dark Prince for decades, and she was fond of looking after him when he was confined to a wheelchair. But eventually, she drifted towards (evil again) Angelus, who could now offer her the chaos and destruction she craved. Notice how she also keeps trying to bring back her family back into place (turning Darla, talking Spike into getting back with her, following Darla's plans to get Angelus back). Dru likes the feeling of her twisted, evil family. And yet, she has no problem leaving them behind / moving on if they're not strong enough or not willing to be part of the family again. What does this mean for Dru slashers?
Many things. For starters, is your female counterpart up to the challenge? Dru may not be the sanest vamp around, but that doesn't mean she's not cunning, smart and strong. Notice how, out of the original Fanged Four, she's the only one who has never had a soul restored in any way, only died once as she was sired, and has more or less remained the same through her unlife. She may like her partners powerful, but she can survive solo. So we'd be talking of someone along the lines of Anyanka, Darla, Glory or Wishverse VampWillow, someone who can hold her own in front of Drusilla. Can they be equals? Maybe, but not likely in the case of Darla, who even now as Drusilla's childe, is still the "elder" one and blood relative as well. This is not too bad for Drusilla, since she also has a strong masochist vibe and enjoys pain. A lot.
Does this means Dru is just to be dragged along by a demoness/vampiress/hellgoddess? Not at all. Like I say, Dru is no fool. She's also quite manipulative, her little ramblings often leading to important parts of the story, whether in a good way (her leading Spike to the cross to restore her health) or bad (her talk about fire, a little before Angel setting her and Darla in flames). If Drusilla wants something, she's likely to get it, using whatever means necessary. She may be lost sometimes in her mind, but she's not completely oblivious to the outside world. Many of her thoughts make sense if you pay attention to what's happening around the character. More importantly, she sometimes can sense things nobody else notices.
Of course, these are not the only options for slashing Dru. Since she's a character that can go so easily from submissive to dominant, the pairing sets the tone of the whole relationship. So a character more submissive (think Fred, Dawn or season one Willow) would work too. It can be a case of infatuations gone bad, or maybe just about corrupting the innocent. Your story, your setting. Keep in mind none of these characters is 100% pure either. If they're with Drusilla, there must be a logical explanation about it.
Last but certainly not least, vampires do not follow normal sexual behavior. Being vamped pretty much opens your eyes to new tastes and pleasures. And Drusilla was taught by the Bonnie and Clyde of the vampire world, Angelus and Darla. So leave the fluff behind on this one. Dru is all about the dark.
In the end, DruSlash. It's good, it's fun, it's possible if you follow the rules, and can be quite pretty.