Here's an attempt to list some of the key issues (first appearances and significant events) to look for in the comic world. I'm building this list gradually so if you have something that you would like to add please comment and I'll try and update the list.
Strange Tales 110 - First Doctor Strange
New Mutants 87 - First Cable
New Mutants 98 - First Deadpool
NYX 3 - First X-23
Hulk 181 - First Wolverine
Edge of Spiderverse 2 - First Spidergwen
Marvel Spotlight 5 - First Ghostrider
Luke Cage Hero for Hire 1 - First appearance of Luke Cage
X-Men 94 - First ongoing series with new x-men team
Werewolf by Night 32 - First Moon Knight
House of Secrets 92 - First Swamp Thing
Giant-Size X-Men #1 (1975) - New X-Men Team
Superman's Pal Jimmy Olsen #134 - First Darkseid
Iron Man #55 - First Thanos
Marvel Premiere #15 (1974) - First Iron Fist
Amazing Adventures #11 (1972) - First App of Furry Beast
Tomb of Dracula #10 (1973) - First Blade
Batman #232 (1971) - First Appearance, Ra's Al Ghul
Marvel Preview #7 (1976) - First Appearance, Rocket Raccoon
Detective Comics #400 (1970) - First Man-Bat
X-Men #101 (1976) - First Appearance, Phoenix
Iron Fist #14 (1977) - First Appearance, Sabre-Tooth
All-Star Comics #58 (1976) - First Appearance, Power Girl
Savage Tales #1 (1971) - First Appearance, Man-Thing
Ms. Marvel #1 (1977) - First Appearance of Carol Danvers as Ms. Marvel
Marvel Preview #4 (1976) - First Appearance, Star Lord
Captain Britain #8 (1976) - First Appearance Betsy Braddock / Psylocke
Marvel Spotlight #32 (1977) - First Appearance, Spider-Woman
Strange Tales #180 (1975) - First Appearance, Gamora
Adventure into Fear #19 (1973) - First Appearance, Howard the Duck
Daredevil #168 (1981) - First Appearance, Elektra
X-Men #120 (1979) - First Appearance, Alpha Flight
Detective Comics #411 (1971) - First Appearance, Talia al Ghul
New Teen Titans #2 (1980) - First Appearance, Deathstroke the Terminator
Batman Adventures #12 (1993) - 1st Appearance of Harley Quinn
Walking Dead #27 (2006) - 1st Appearance of the Governor
Batman Vengeance of Bane Special (1993) - 1st Appearance of Bane
Walking Dead #19 (2005) - 1st Appearance of Michonne
Walking Dead #100 (2012) - 1st Appearance of Negan
Marvel Super-Heroes #8 (1992,"Winter Special") - 1st Appearance, Squirrel Girl
Starman 9 - First App of Blockbuster (The real one)
Aquaman 19 New 52 - King Nefareus (Villain in Aquaman Movie)
X-Men 49 - 1st Polaris
Amazing Spider-Man #101 (1971) - First Morbius the Vampire
Amazing Spider-Man #122 (1973) - Death of Green Goblin
The Amazing Spider-Man #129 (1974) - First Punisher
Amazing Spider-Man #121 - Death of Gwen Stacey