The results of field surveys, velocimetric records, and numerical models are reported with the goal of analyzing the local seismic response in a section of the Nera River alluvial valley in central Italy. Alluvial deposit geometry and dynamic properties were defined by geological and geophysical investigations. 2D amplification effects were pointed out by horizontal-to-vertical spectral ratios (HVSRs) as well as by horizontal-to-horizontal spectral ratios (HHSRs) to a reference station; HVSRs were derived from both noise and weak-motion records, while HHSRs were only computed from weak motions. Where travertine deposits are interlayered within the alluvia, 2D amplification effects are shown only by HHSRs. The observed amplifications: (1) consist of peaks of the amplification functions A(f) in the range 1–10 Hz, (2) generally correspond to two frequency ranges whose values mainly depend on the valley shaped ratio and on the local heterogenities of the alluvial deposits, and (3) can be regarded as due to a 1D resonance combined with lateral wave propagation. Numerical models via the finite difference method were performed by the Italian National Institute for Geophysics and Volcanology Web Interface for Seismological Application and by the Fast Lagrangian Analysis of Continua codes. The obtained results: (1) show a good agreement with HHSRs, (2) prove that some 2D amplification effects are constrained by both the shape ratio of the valley and the heterogeneity of the alluvial deposits, (3) reveal focalization effects within the alluvial deposits strictly related to the shape of the valley, and (4) allow the comparison of the A(f) functions in both linear and nonlinear dynamic behavior and the computation of the shear strains due to ground motion within the alluvial deposits.