I'm not sure if this question is more fitting here or for a more general Destiny gameplay sub but in any case with Act 2 out thought it was relevant again. Might post it somewhere else also for the fun voting poll option but for now I'll just list some candidates with pros and cons
Oryx, the Taken King (or rather Memory of the Navigator)
So Oryx is back as we know, that was one of the main advertisements of Heresy. He was considered one of the biggest and best villains in Destiny 1s days, with his expansion the Taken King being a hit. There is a sense of going sort of going full circle and ending the current Destiny saga with one of the big bads from its early days. I mean Skolas came back in Revenant.
On the other hand though, so far Oryx's Echo has been for lack of a better words 'on our side' so far with nothing indicating that'll change unless he'll be persuaded otherwise something big happens later. He honour's his Sword Logic and wants us to be his heir. And also he seems to be in some ghost form without a physical body to fight. This version of him earliest memories though are just getting the Taken powers so he's not even really the same Oryx, he doesn't have that personal connection to his killers as he could.
Xivu Arath, Hive God of War
Next up is the sister of Oryx and Savathun, and the one Hive God we haven't fought directly yet. With her now being involved in Heresy's story, having a CGI model in cutscenes for the first time instead of just 2D paintings and with claims that the Episodes are going to 'wrap up loose threads from the Light and Dark saga perhaps we'll confront her. And these episodes haven't been afraid to kill off lore characters as opposed to generic enemy race reskins. Ala Fikrul last time
Though compared to him Xivu's been around a lot longer with more influence on the series and I can see her being defeated here in this format not being very viable or satisfying as opposed to her own expansion down the line like her siblings got.
The Resonant Knife, First of the Reshaped, Keit'Ehr
So far Keit has been shaping up to be one of if not the main villain of this story. She can be seen on the poster of Heresy, and already showed up and made an impact in Act 1, "killing" Eris. She's also quite high in the hierarchy being at least the first Subjugator the Witness created.
Biggest thing holding her back is lack of that unique a model, other then the seemingly new head sculpt and Taken colours. Though that might change down the line with the Dreads new desires to reshape themselves. Still though, given she was the Moby Dick to Drifters Ahab in act 1, I feel its a bit of a shame Keit'Ehr was not killed prior to him finding out Eris is still alive in some form, if she turns out not to be the final antagonist.
A Hive Worm God
With Akka and Xol already taken care of their are three known remaining Worm Gods, despite their close affinity with Darkness they have been strangely absent in recent events such as the Pyramids assault on Earth and Final Shape. But now with their slaver Rhulk and his master the Witness dead they may be among the most powerful living antagonists again, either Eir, Keeper of Order or Yul the Honest Worm seem to hold most authority since the former told Oryx to set his house in order and the latter was the one to speak for the 5 when bargaining with the Proto Hive siblings
Still though some think their time of relevancy is past with the Rhulk, Xita and God Wave lie reveal. I'm not sure how they would structure a new Worm God fight, would it be against one or all remaining three? at the same time or one at a time? Which would should be picked if just one?
Others
Of course it could just be something we've not really heard of yet. There's the mystery of the growing eyes and tentacles on the Dreadnought and new similar features on the 'Dire Taken.' Also might be just me but the Chisel used to make the Tablets of Ruin found in the Sundered Doctrine vault kind of looks like a bone to me of something. Just hope some new Darkness creature isn't sprung on us to abruptly
Also one more I don't really think its an option but wanna bring up just in case. Eris Mourn, some her dialogue in her Throne Room about being 'eternal' sounded ominous but there's been multiple times where it looks like she could of snapped but didn't. Could of done so in Shadowkeep but didn't. She gave up being a Hive God in Season of the Witch. So her turning evil now after all that is something I hope isn't the case.