The expression for the determinant of a block matrix is
$$A = \left(\begin{array}{cc} B & C \\ D & E \end{array}\right)=\mbox{det}(B)\mbox{det}(E-DB^{-1}C)$$
where the matrices $B,C,D,E$ can be the $2\times2$ matrices you mentioned. You can find it here https://en.wikipedia.org/wiki/Determinant#Block_matrices Be careful! this expresion is only working if $B$ is invertible ($\mbox{det}(B)\ne0$). If $C=0$ or $D=0$, this expression simplifies to $\mbox{det}(B)\mbox{det}(E)$. So, an intelligent strategy is the use of gaussian elimination to simplify the matrix to this form and to get a simpler problem.
Finally, if the matrix has many zeroes in a column or a row, it is convenient the use of minors to compute the determinant http://mathworld.wolfram.com/DeterminantExpansionbyMinors.html which involve the computation of only $3\times3$ determinants. I hope this will be helpful!