Oddworld: Stranger's Wrath HD

Story-related. Cannot be missed.
Once you’ve cleared the Water Facility of all Outlaws, Duke will appear on the roof of a building with two Outlaw Mortars, who you must take out first. Head inside the small building directly behind you (opposite the building where the Mortars are) where you will be safe from their fire. Use Fuzzles to defeat them.

Once they’re down, Duke will appear at ground level and will start shooting his machine gun at you. Run and jump to get away from him and wait behind the large stones opposite the entrance. Equip the Zappfly and Thudslugs on your crossbow and wait for Duke to come to you. When he is within your sights immediately fire with the Thudslug and charged Zappfly to knock him back. Your aim is to push Duke towards the side of the facility to minimise the chance of you knocking him into spikes or one of the giant fans that are in the facility. You will have to alternate fire between each ammo type due to the slow reload time of the Thudslug. Keep an eye on Duke’s stamina bar (the blue bar) and do not stop firing until it has depleted. His stamina will recharge very quickly so fire your ammo as soon as it is ready. Once Duke’s stamina has depleted he will be unconscious with three gold stars circling his head. Quickly bounty him before he wakes up.

As mentioned there are spikes and giant fans in and around the facility. Shoot Duke with a Thudslug in front of one of these and he will die instantly. Use this method if you wish during your Hard playthrough only.