I have a $2n \times 2n$ matrix, $M$. I view it a block matrix, of $n^2$ blocks, each of shape $2\times 2$. Computing the determinant of $M$ is easy by conventional methods. I could also look at diagonal block submatrices: given a set $S \subseteq [n]$, I take the submatrix of all the rows in $S$ and columns in $S$.
For instance, if $n=3$, I have 9 blocks (each of 4 entries), $A_{1,1}, A_{1,2} \dots A_{3,3}$. $S$ could be ${1,3}$, in which case I take the 4x4 submatrix
$$\begin{bmatrix} A_{1,1} & A_{1,3} \\ A_{3,1} & A_{3,3}\end{bmatrix}$$
There are $2^n$ such submatrices, and each has its own determinant. I would like to compute the sum of those determinants as efficiently as possible. (The trivial case, where $S = \emptyset$, naturally has a determinant of 1.) This might sound like a bold hope, but consider that if this were not a block matrix, then you can very easily compute the sum of the determinants of the diagonal submatrices:
$$ \sum_{S \subseteq [n]} M_{S,S} = \det(M + I) $$
So I'm hoping that there's some way to make a good "block identity matrix" that I can carry out operations with to compute this sum. Honestly, I'd be happy with anything in polynomial time.
Proofs of hardness would also be interesting. For instance, I could believe that the problem of computing the permanent might somehow be reduced this problem, in which case it would be NP-Hard. I have several fairly different approaches that take $2^n$ time, so anything in even $1.9^n$ would be stimulating.