Hi, iankms—Since "if" governs the two clausal conjuncts and there is a conditional relationship between those conjuncts (Nick's being right would imply the truth of the second conjunct), they should be balanced in mood:
(1) What if Nick were right(,) and twelve were the most boring number?
(2) What if Nick is right(,) and twelve is the most boring number?
I've placed the comma in parentheses to show that it is optional; it can be used or not. Using it won't change the need for balance between the clauses in their mood. Using the comma and changing the mood will change the meaning:
(3) What if Nick were right, and (what if) twelve is the most boring number?
In (3), there is no conditional relationship between Nick's being right and twelve's being the most boring number; (3) asks two separate questions. Whatever Nick may be right about, it needn't be about the number twelve.
(4) What if Nick were right that twelve is the most boring number?
(5) What if Nick were right about twelve's being the most boring number?
(6) What if Nick is right that twelve is the most boring number?
(7) What if Nick is right about twelve's being the most boring number?
All four of those sentences, unlike your second example in the OP, are correct. There is no question of imbalance in mood in any of them. In (4) and (6), the "that"-clause complements "right." In (5) and (7), the second clause is nonfinite.