I think I'd have it be a River-centric episode, where she sees the end of his life (much like he saw her die in The Library). Make it the last River episode ever. I know she's probably traveled around with future Doctor's but to me her story will be forever tied to the Eleventh Doctor, so even though she knows other Doctors, we don't necessarily need to see it.
I'd even mix things up and make it a quieter, more character-driven story. Lay off the sonic screwdriver and the running and the big monsters. Make it more personal.
I wouldn't have a River centric episode, but maybe she should be in it. Why not make her the dominant companion for a couple of episodes and dump Clara off at home for a few episodes like Martha, but she'd go back to being the main companion after. It'd be fun to see Clara's reaction to the doctor changing.
And yeah, I'd make it the last River episode. What I'd like to do to make sure she'd not come back is make it so she's wearing her space suit she did in the 10th doctor story and she reveals "I'm going on a mission for a while, we'll see each other again" although the doctor knows he won't, which would bring in a nice tragic element to the episode.
But I wouldn't have a quiet one. It'd be a big episode. Maybe we'd see the origin of the real cybermen, I'd love to see an episode of doctor who one day where we see the cybermen before and after their transformation into cybermen. We'd get to see the old cloth face ones again, but they'd have to make it more realistic by making the human hands sort of greenish so we know there's no blood flow, and there'd be like small fragments of blood on their cloth faces left over from operating. Maybe that'd serve as a great regeneration episode. I know the title would be parodying, but Genesis of the Cybermen would work as the title.
I wouldn't want her to know any of the other doctors. I'd like it to remain that it's just 11 and at the end of her life, 10 that she knew.