Let's see here...

> Having Ron leave, either because he's finally seen that in dire times, he doesn't have as strong of a bond with Harry and Hermione as they used to, ex: he wants to keep his family safe and if he's with Harry he can't do that. He could go to the Dark Lord and convert in exchange for his family's safety and possible insights to what Harry and Hermione have been up to, in terms of progress and whereabouts.

> In any instance, he probably would be killed off at some point, so we might as well make him evil, or rather fed up with Harry.

> I wouldn't necessarily say Hermione would resent Harry, that's a strong word. But she could be growing more weary as there's no light at the end of the tunnel. She'd probably stay with him out of strained friendship and with Ron gone, perhaps out of guilt. If I have her harboring feelings for Harry, his interactions in the past with Cho and Ginny could probably boil over, depending how you write him in relation to Ginny.

> If we're starting before or when Ron leaves, we could have Draco x Luna at school, with him already planning to do something with her. The question is whether to kidnap her or not, as how he approaches her will probably dictate their relationship. If he approaches her with an offer with valid points, it may make her convert more smoothly than if he held his wand to her throat.