I could honestly see the story branching off either way: she returns in some form or fashion, or she doesn't as a lesson to humanize Chief. Some folks mentioned the possibility of her return as an organic/human woman. Others mentioned the possibility of some fragment of her existing in full on rampancy (thus making her an enemy and possible servant to the Didact--who, for some reason I don't think it truly perma-dead yet). Those are cool ideas. I have to say I hope she does make a return in some way--well handled ofcourse. But no matter what, since this series is mostly about the development of John's character, and since Cortana is basically the key to his humanity, she'll play an important role in future games (whether she's alive or dead).
I don't really agree that Cortana returning to the series would definitively be detrimental, cheesy, or unoriginal. I think it could be a very good thing (if handled well....and I think the folks at 343 are up to it). There's certainly enough reason to believe it's possible so it's not like we'd be invoking space magic to make it happen. It's not a necessity to the future happiness we all hope John to have someday--but it'd definitely be a super awesome plus! Personally, I'd be really, really happy to see her return in the series (though hopefully their relationship would undergo some kind of dynamic change--I agree that things shouldn't go back to being the way they always were.) I think her being a temporary enemy then eventually becoming metastable or even human/organic would be pretty cool! And if I'm allowed a small miniscle moment of shameless shipping, it would make my heart smile to see a happy ending with John and Cortana alive and well.
My personal opinion is that a happy ending is the new original. Everybody's pulling out these bittersweet, emo-drenched, kinda-depressing, slightly pessimitic, "nobody-gets-what-they-want-because-lifes-just-not-like-that" sacraficial endings......so, it'd be a refreshing change of pace to get a relatively happy one where the lovers/best friends/partners/ or-whatever-else-they-pass-for are reunited and...well...happy. I endured Mass Effect 3 with dignity, appreciation, and respect....but to be honest, I've filled my artistic integrity quota for the next 5 years. Now I just want happy.
But no matter what, I have to say I greatly appreciated the dedication to character development this game brought. While I appreciated Chief and Cortana's relationship, I never gave it as much thought until I played Halo 4. I viewed Chief as more of an impersonal force who occasionally acted like that man prior to this. A really awesome, yet kind of tragic impersonal force. Chief's had to deal with the death of soldiers all his life: Johnson, Miranda Keyes, etc. That's totally within his comfort zone. But to lose Cortana--that's worldview shattering. 343 did a good job--there really is a man under there afterall. I loved it!! I'll love it more if Cortana isn't perma-dead....but I'll silence the shipper inside if she is.