It's really any program. It is most useful for all those that use any value defined as environment variable. You can pass an environment variable value to any program without actually setting it in your shell (and thereby influencing other programs down the line).
env ls runs ls without modifying the environment. env -i ls resets the environment. On my system, this removes colors from its output, since it unsets LSCOLORS and CLICOLOR. env LSCOLORS=GxfxcxhxdxegdggbgdAhAg ls will run ls, passing the specified LSCOLORS string and possibly changing how the ls output is colored.