We demonstrate that a nanostructured metal thin film can achieve enhanced transmission efficiency and sharp resonances and use a large-scale and high-throughput nanofabrication technique for the plasmonic structures. The fabrication technique combines the features of nanoimprint and soft lithography to topographically construct metal thin films with nanoscale patterns. Metal nanogratings developed using this method show significantly enhanced optical transmission (up to a one-order-of-magnitude enhancement) and sharp resonances with full width at half maximum (FWHM) of ~15 nm in the zero-order transmission using an incoherent white light source. These nanostructures are sensitive to the surrounding environment, and the resonance can shift as the refractive index changes. We derive an analytical method using a spatial Fourier transformation to understand the enhancement phenomenon and the sensing mechanism. The use of real-time monitoring of protein-protein interactions in microfluidic cells integrated with these nanostructures is demonstrated to be effective for biosensing. The perpendicular transmission configuration and large-scale structures provide a feasible platform without sophisticated optical instrumentation to realize label-free surface plasmon resonance (SPR) sensing.