South Park: The Stick of Truth

Any%

• Mage is picked because of Dragon's Breath - it clears multiple enemies insanely quickly, is quick to use, and synergises with many other elements you pick in your run.
• Speed Potions are your primary consumable, and in many fights you can use them to kill the enemies before they get a single turn. Knowing how many you will use and when allows you to plan when to buy them.
• Butters is your primary companion of choice until you get Kyle. Butters has decent single target DPS, a multi-target spell that is useful in one early fight before your Dragon's Breath hits multiple targets, and his heal synergises with the "Brain Food" perk - it does 3 ticks of healing, which each restore 2 PP with Brain Food.
• Once you get access to Kyle, however, he's your main choice. His Summon Ike ability does insane single target DPS, which is the majority of fights you encounter after you get him. He lets you kill the Bishop of Banff before he can heal, and Craig before he can split, saving lots of time. For these reasons, you side with the Drow Elves instead of Kupa Keep. Sorry Cartman. This does mean you have four fights (against Butters, 6th Graders and several Nazi Zombies) where Stan is your buddy, but they're quick fights made easy with Speed Potions and Dragon's Breath.
• The vast majority of fights can be skipped altogether. There are 30 unskippable fights. Everything else can either be negated by the environment or straight up run past. This is your major timesaver, and the main distinction of a speedrun.
• Your gear is largely dictated by what the story makes you wear, or what you're automatically equipped with. The only times you'll stop to equip something not required by the story are when you hit level 8, and can equip the SWAT helmet (gives you an extra attack when you kill an enemy, super strong), and to requip your usual gear after wearing something required for the storyline (Alien ship, when you're shrunk by gnomes, after leaving the abortion clinic, being goth etc.). You vey rarely go out of the way to pick up certain items of gear, if any at all. In fact, the only things you buy or specifically pick up are the lv4 Club of Smiting from Scott at Kupa Keep (speeds up the Bard fights), the SWAT helmet, and a Weightlifting Patch from Mr Mackey. You often equip the only patches you ever get from storylines.
• The only sidequest you complete is getting the Mr Slave Summon early in the the game, which you use once to beat the Elven Antimage at Jimmy's house. This times out as 7s faster than beating the Antimage without Mr Slave. Plus it's funnier.
• Ability and perk-wise, you need to make sure you get 7 friends ASAP for the Brain Food perk. You should get 12 rather quickly through the story, allowing you to pick up Pyromaniac. They're the only two you'll ever really need. As Dragons Breath is the only ability you use, it's the only one you need to level, and you max it as soon as you can. You will get it to max level before fighting Jimmy, who is the first enemy with an appreciable armor value.
• You can/should skip Mr Slave's Ass.