With its potential for ultrasensitive, label-free detection of molecular interactions, sensing methods based on the surface plasmon resonance (SPR) effect fully meet the requirements for modern analytical techniques. Already established as using propagating SPR in thin gold layers, the last years witnessed the emergence of another technique utilizing extremely miniaturised noble metal sensor structures, based on a localized SPR. This paper provides a critical comparison of these various kinds of SPR sensing, reviews the foundation of both general approaches, presents experimental data on exactly the same model system using bot techniques, as well as theoretical considerations in order to allow for a reasonable comparison. It highlights the specific features and effects, in order to provide guidance in choosing the right technique for a given bioanalytical tasks. The study yielded that for the detection of quite small (bio)molecules, smaller particles are favored regarding highest sensitivity. It also presents an approach to obtain refractive index and the thickness of a molecular film by analysing the signal response of plasmonic sensors with metal nanoparticles. Also, an additional method for the improvement of the parameters’ determination is introduced.