Roadmap

Step 1 - Play on Human: Start on Human difficulty as difficulty trophies do not stack. This is the best time to collect all Blue Orbs/Fragments, Purple Orbs/Fragments, and complete Secret Missions. Also, attempt mission-specific trophies like killing all enemies in the first mission. You can begin working on S Ranks, as Human difficulty has lenient requirements. Do not use any continues to maintain a 1.2x multiplier. Getting the No Hit bonus is unlikely on a first playthrough but guarantees an S Rank.

Step 2 - Play on Devil Hunter: Replay the game on Devil Hunter difficulty. Enemies have double the health and deal double the damage compared to Human, but enemy types remain the same.

Step 3 - Play on Son of Sparda & Skills: This difficulty unlocks after completing the game once. Enemies have four times the health and deal four times the damage of Human difficulty. Expect different enemy spawns, such as an Empusa Queen in the Prologue. Completing this difficulty unlocks a new skill for Dante, necessary for the all skills trophy. Replay this mode to familiarize yourself with enemy patterns before Hell and Hell. Farm Red Orbs for all skills, ideally using the last checkpoint (an auto-save point you restart from on death) in Mission 13 with the Dr. Faust weapon upgraded (Dr. Faust 4) and Hat Trick ability. Use R1/RB then Circle/B in an area with nests and enemies. Restart the checkpoint when few enemies remain. This farming can also be done on Human difficulty if you get hit. It may take several hours to acquire all necessary Red Orbs.

Step 4 - Play on Dante Must Die: This is a significantly harder difficulty. Enemies have eight times the health and deal eight times the damage of Human difficulty, with aggressive enemy spawns from Son of Sparda. Ensure you have farmed Red Orbs for all skills beforehand. Use Gold Orbs for reviving if needed, but focus on learning enemy patterns first.

Step 5 - Play on Heaven or Hell: In this difficulty, both you and enemies die in one hit, including bosses. Use ranged attacks and hang back. This is an ideal opportunity to defeat the Prologue boss if you missed the trophy/achievement earlier.

Step 6 - Play on Hell and Hell: The hardest difficulty. You die in one hit, while enemies have the same health as on Son of Sparda. There are no checkpoints, only three lives per mission, and no option to revive using Gold Orbs or Red Orbs. Getting hit three times forces a mission restart. S Ranks are challenging but possible with up to two hits, and score requirements are similar to Son of Sparda.

Step 7 - Cleaning Up: Obtain any remaining trophies/achievements, including S Ranks on all difficulties (except Heaven or Hell) and any miscellaneous trophies not yet acquired.