We study the prospects for detecting the annihilation products of dark matter (DM) in the framework of the two highest-resolution numerical simulations currently available, i.e., Via Lactea II and Aquarius. We propose a strategy to determine the shape and size of the region around the Galactic center that maximizes the probability of observing a DM signal, and we show that, although the predicted flux can differ by a factor of 10 for a given DM candidate in the two simulation setups, the search strategy remains actually unchanged, since it relies on the angular profile of the annihilation flux, not on its normalization. We present mock γ-ray maps that keep into account the diffuse emissions produced by unresolved halos in the Galaxy, and we show that, in an optimistic DM scenario, a few individual clumps can be resolved above the background with the Fermi-LAT. Finally, we calculate the energy-dependent boost factors for positrons and antiprotons and show that they are always of O(1), and, therefore, they cannot lead to the large enhancements of the antimatter fluxes required to explain the recent PAMELA, ATIC, Fermi, and HESS data. Still, we show that the annihilation of 100 GeV weakly interacting massive particles into charged lepton pairs may contribute significantly to the positron budget.