I've had some interesting thoughts lately on evaluating cards for inclusion in the cube and encouraging interactive games. Basically, we don't want (too many) games to feel like coin flips where being on the play is an automatic win.
I assume that the player who goes first plays any 1/1. To evaluate cards I then ask:
a.) Can this one-drop stop the player on the draw from dying?
b.) Can this two (or one) drop win player 1 on their second turn?
For a., spells seem to be better than creatures. Killing the opponent's one drop with Wring Flesh, Fiery Impulse, or Blazing Volley makes it impossible to die on turn 2. Healing Grace should be enough to survive any opening attack, and Radiant Fountain (essentially a one drop on turn one) survives almost any attack but puts you in pretty rough position. And if your opponent leaves up one blue without conceding, they must be sitting on a Select for Inspection (great time for Duress, or Miscast/Unsubstantiate in a blue mirror).
The other options are creatures; either another 1/1 to trade, or one of the defensive 0/X creatures to block. The 1/1 blockers will still die to Wring Flesh, Fiery Impulse, and Blazing Volley, making those very good spells on attack or defense.
P2 gets access to 2 drops as well to negate P1's defensive play and win outright. P2 can trample over a 1/1 with a Duskshell Crawler played after any non lifelinking 1/1. P2 can also bounce any creature with callous dismissal, kill all but Aegis Turtle or Wall of Runes with Abrade, or if heavy in black, Pharika's Cure for an overkill kill.
I think it's okay to have some number of 2-card combos in the cube but care must be taken to make sure they can't be forced in the draft. When evaluating cards for draft, one-drop removal like Wring Flesh and Fiery Impulse that are incredibly powerful on both play and draw should be prioritized. When evaluating cards for the CUBE, be wary of these. I'd love to see the spell balance tip more toward one-drop defensive interaction that isn't great on offense, like Select for Inspection and Healing Grace. Also we'll have to wait and see if we want both Unsubstantiate and Callous Dismissal both in the cube as they can blowout creatures on turn 2. Blue is intended to be largely defensive but its two drops have great offensive potential at the moment.
Since this is grid draft, you can hate draft or draft against what your opponent is doing, meaning that the cube is likely to feel balanced as long as there isn't too much redundancy for broken parts. I don't necessarily want the cube's power level to be totally flat, but time will tell if some options are oppressively stronger than others, and if there are cards that just aren't seeing play (I've yet to draft a deck that wanted Pharika's Cure; those pips are insufferable).
Here are some 2-card interactions to keep in mind while drafting, mulliganing, and playing.
Duskshell Crawler + any 1/1 = trampling over any other non-lifelinking 1/1 on turn 2. Wildwood Tracker is especially punishing.
Arcbound Javelineer + Titanic Brawl = Can survive the fight on turn 2 and follow up with an attack
Mage Duel + One drop Spells = Allow your creature to fight theirs and survive before following up with an attack. Require 3 cards in your opening hand which can be rough.
Arcbnound Javelineer + Titanic Brawl = Javelineer can not only survive a fight with a 1/1, it even gets to use Titanic Brawl's cheaper mode (though that's just win-more at that point).
Snakeskin Veil + Titanic Brawl = Both can be played on turn 2, but that requires double green so it will only benifit an Elvish Mystic or Wildwood Tracker.
Spear Spewer + Healing Grace/Revitalize/Environmental Sciences/Radiant Fountain: Spear Spewer combo seems really hard to deal with if it's on the play, especially since half the lifegain enablers for a T2 kill aren't even in white.