Death Spheres are part of the defense system employed by Maliwan on Skywell-27. There are several different types: Overspheres, Harbingers, Stingers, Defenders, and Offenders. Rhys tells the Vault Hunters to hijack one using a Viper Drive so they can get into the main control room of Skywell-27's giant laser. (However, they mistakenly hijack a Pleasure Sphere instead.)
At the end of the Space-Laser Tag story mission, the Vault Hunters have to fight the Katagawa Ball boss, which is a large and well-shielded Death Sphere.