Refractive index sensitivity of guided resonances in photonic crystal slabs is analyzed. We show that modal properties of guided resonances strongly affect spectral sensitivity and quality factors, resulting in substantial enhancement of refractive index sensitivity. A three-fold spectral sensitivity enhancement is demonstrated for suspended slab designs, in contrast to designs with a slab resting over a substrate. Spectral sensitivity values are additionally shown to be unaffected by quality factor reductions, which are common to fabricated photonic crystal nano-structures. Finally, we determine that proper selection of photonic crystal slab design parameters permits biosensing of a wide range of analytes, including proteins, antigens, and cells. These photonic crystals are compatible with large-area biosensor designs, permitting direct access to externally incident optical beams in a microfluidic device.