Anyone else have something similar to this happen to them? BTW... I also have had Serana invincible since, I assume, forever. Either that, or ever since I took her back to Dimhollow Crypt/Cavern after clearing that cell out quest-wise.
I fast traveled to the Sun Stone, told her to wait about 15 ft before the Ash Spawns that are in the area, walked up to the Ash Spawn and summoned a Frost Atronach, and proceeded to attack them, but she intervened any how. During the fight I she accidentally attacked the Frost Atronach with Hevnoraak's Staff (Wall of Storms)... The Atronach became hostile to her, but as I said, she's invincible (she can't be damaged, hurt, killed, made to drop down to one knee, OR even effected in as small of a way as being walked into so that she moves out of your way so you can get by her (or maybe that last part is just plain normal... I don't know)), so the Atronach just ended up disappearing after it's time ran out. After which, that's when I went back over to her and told her to follow me again and a few seconds passed by while I looked around (4-5 seconds) then she said "Where'd you come from?" like another enemy popped up again, but as it turned out after about 30 seconds of running around like a chicken with it's head cut off trying to figure out where the Destruction Spells were coming from and where the red dot on my radar was located, I got hit hard by a Shock Spell and realized who was actually attacking me and of course since she's been invincible I couldn't do anything except die, nor did I have much more time to try anything else out to fix it (like by fast traveling) or anything.

Ultimately though, upon respawning from the reload there was no more hostility from her since then.

WTF??...??? O_o

Any other similar issues out there?

not sure if this belongs in the dragonborn section
ive had this happen twice with her becoming randomly hostile without db installed so its not a db issue
i think its just a little bug in her coding
has happened with a few other followers too

I ditched her, she is not worth the trouble.

I was doing a quest in the dragonborn areas, where I kept thinking that the guy I had to kill in a dungeon was turning me into a "super" vampire, a form where I was instantly a vampire at the first stage without being able to cure it.

Upon loading the save before I entered, 3 times, I finally figured out it was the flying red stuff/blood svcking of Serena. The dude was not even a vampire!

I also got no option to cure it, from that one quest guy you can cure it from.

It was then that I got rid of her. First, I just tried to cure her. Unfortunately, this makes her so she no longer has an option to group with you (once cured.)

I got that Frea lady instead, from the dragonborn expansion. She isn't quite as cool, but I've got her all in stol/whatever plate armor with an axe and something and she does very well.

Not sure what you mean by had her invincible; Like Frea, and Mjoll the Lioness, she is "essential" so she can't die. However, I believe mine did go to one knee? (as the other two will, if hurt enough.)