Predictions vary from silly to edgy, and may be completely contradictory. Under the cut for potential spoilers.

Hiveswap:

Joey will perform in the troll version of American Idol with Xefros and win.

Joey and Xefros will play a game of Alternian sports and win.

Joey and Xefros will play a game Alternian paintball with a group of clown cultists.

Joey will never fire a gun in the game.

Joey will definitely need to fire a gun, but only at the very end of the game.

Doc Scratch will try to manipulate Joey into overthrowing Trizza to make way for Feferi.

Joey will get a girlfriend before the game ends.

Trizza doesn’t actually hate aliens and will become Joey’s girlfriend.

Joey will kill have to kill Tizza to save Xefros’ life.

Joey and Xefros will comes across one of the meteor trolls, and the player will be allowed to pick it up and name it (it will probably be Karkat).

Byers will survive to the end of the game, but the pogs will not.

Hauntswitch: (Most of this is Guardian related, sorry)

Jude and Dammek will have a dynamic similar to Dib and Zim.

Dammek will have a satisfying character arc and learn to be less of a dick (but still be a little bit of a dick).

Jude and Dammek will have to infiltrate and destroy an Earth clown cult.

We will learn more about the history between Mom!Roxy and Grandpa!Jake.

The room behind the Mummy door contains secrets about Mom!Roxy.

Grandpa!Jake actually raised both Mom!Roxy and Bro!Dirk, but things ended badly due to a variety of circumstances (such as Jake’s marriage to A. Claire, or Lil’ Cal’s influence on Dirk).

Grandpa!Jake meant to take in Bro!Dirk along with Mom!Roxy, but was never able to find him because of Reasons.

Grandpa!Jake has been to Alternia and that Signless doll was based on accounts by real Sufferer zealots.

Bro!Dirk created the Manthro Chaps toy line in addition to Smuppets, and Grandpa!Jake may or may not hold the distribution rights. 

We will see a picture of Bro!Dirk as a child with Lil Cal in a similar pose to that one picture of Andrew Hussie with the creepy puppet.

Grandpa!Jake, Mom!Roxy, and Bro!Dirk will appear in the game as either allies or boss fights depending on who meets them (they are Adults and Dammek will shoot before asking questions).

Overall:

Joey, Jude, Xefros, and Dammek will all be transported to Earth C somehow and survive the apocalypse. (Joey will punch Jake in the face if she ever meets him.)

Joey, Jude, Xefros, and Dammek will enter their own game of Sburb along with whoever Grandpa!Jake could save with his version of Sburb.

Joey, Jude, Xefros, and Dammek will all die and everything will be terrible forever.