《蜘蛛侠：敌友难辨》的故事主线会与蜘蛛人（彼得帕克）以及他的好友绿魔人二世（哈里）脱不了关系。原本是好友的两个人，却因为蜘蛛人与哈里的父亲绿魔人一世的战斗意外让哈里的父亲误伤自己而亡，哈里也误会自己的好友为杀自己的父亲，化身为绿魔人二世展开复仇，而这是最好体现游戏名称《蜘蛛侠：敌友难辨》的目的。
| 序号 | 图片 | 名称 | 描述 | 积分 |
| 1 |  | Tokyo Complete | Find all collectibles, find all secrets, and defeat all bosses in this location. | 125 |
| 2 |  | Tangaroa Island Complete | Find all collectibles, find all secrets, and defeat all bosses in this location. | 125 |
| 3 |  | Egypt Complete | Find all collectibles, find all secrets, and defeat all bosses in this location. | 125 |
| 4 |  | Transylvania Complete | Find all collectibles, find all secrets, and defeat all bosses in this location. | 125 |
| 5 |  | Nepal Complete | Find all collectibles, find all secrets, and defeat all bosses in this location. | 125 |
| 6 |  | Lightning Strikes | Obtain a Hit Chain higher than 15. | 25 |
| 7 |  | Combo Meter Master | Fill the Combo Meter all the way to Level 4. | 25 |
| 8 |  | Our Powers Combined | Initiate a Hero Strike Power-Up. | 25 |
| 9 |  | Web Slinger | Fully upgrade Web Line with all available Modifications. | 75 |
| 10 |  | Arachnid Artillery | Fully upgrade Web Shoot with all available Abilities and Mods. | 75 |
| 11 |  | All Tied Up | Fully upgrade Web Stun with all available Abilities and Mods. | 75 |
| 12 |  | Fury's Fourteen | All characters are fully upgraded with all Attacks and Attributes. | 75 |
