Collisions between prolate uranium nuclei are used to study how particle production and azimuthal anisotropies depend on initial geometry in heavy-ion collisions. We report the two- and four-particle cumulants, v_{2}{2} and v_{2}{4}, for charged hadrons from U+U collisions at sqrt[s_{NN}]=193 GeV and Au+Au collisions at sqrt[s_{NN}]=200 GeV. Nearly fully overlapping collisions are selected based on the energy deposited by spectators in zero degree calorimeters (ZDCs). Within this sample, the observed dependence of v_{2}{2} on multiplicity demonstrates that ZDC information combined with multiplicity can preferentially select different overlap configurations in U+U collisions. We also show that v_{2} vs multiplicity can be better described by models, such as gluon saturation or quark participant models, that eliminate the dependence of the multiplicity on the number of binary nucleon-nucleon collisions.