Separating quantum and classical efficient computation
Establish whether the class of problems solvable efficiently by quantum algorithms with bounded error (BQP) is strictly different from the class of problems solvable efficiently by classical algorithms; for example, show the existence (or nonexistence) of a decision problem in BQP that is not efficiently solvable by any classical randomized algorithm.
References
We don't really know if quantum computers are any different from classical computers, but we highly suspect they are.
Shortly after, Fortnow and Rogers asked if the same is true relative to a \emph{random} oracle, a problem that remains open today.
Quantum computers challenge the Strong Church-Turing thesis, but it remains unproven whether they can be efficiently simulated or not.
There is currently no general theory of speed-ups. While algorithms such as Shor's are generally believed to be robust examples of exponential speedups, there is no classification of speedups in which to place the SQU test.