We consider the model problem of mixing of passive tracers by an incompressible viscous fluid. Addressing questions of optimal control in realistic geometric settings or alternatively the design of fluid-confining geometries that successfully effect mixing requires a meaningful norm in which to quantify mixing that is also suitable for easy and efficient computation (as is needed, e.g., for use in gradient-based optimization methods). We use the physically inspired reasonable surrogate of a negative index Sobolev norm over the complex fluid mixing domain Ω, a task which could be seen as computationally expensive since it requires the computation of an eigenbasis for L2(Ω) by definition. Instead, we compute a representant of the scalar concentration field in an appropriate Sobolev space in order to obtain an equivalent definition of the Sobolev surrogate norm. The representant, in turn, can be computed to high-order accuracy by a Padé approximation to certain fractional pseudo-differential operators, which naturally leads to a sequence of elliptic problems with an inhomogeneity related to snapshots of the time-varying concentration field. Fast and accurate potential theoretic methods are used to efficiently solve these problems, with rapid per-snapshot mix-norm computation made possible by recent advances in numerical methods for volume potentials. We couple the methodology to existing solvers for Stokes and advection equations to obtain a unified framework for simulating and quantifying mixing in arbitrary fluid domains. We provide numerical results demonstrating the convergence of the new approach as the approximation order is increased.