An image sensor may be formed from a planar semiconductor substrate. The image sensor may have an array of pixels. Each pixel may have a photosensitive element that is formed in the substrate and may have a light guide in a dielectric stack that guides light from a microlens and color filter to the photosensitive element. The light guides in pixels that are offset from the center of the image sensor may be tilted so that their longitudinal axes each form a non-zero angle with a vertical axis that lies perpendicular to the planar semiconductor substrate. These light guides may have laterally elongated openings that help collect light. A light guide may have a lower opening that matches the size of an associated photosensitive element. Photosensitive elements that are laterally offset from the center of the image sensor may be tilted. Pixels of different colors may have off-center photosensitive elements.