I encourage anyone who's a hardcore sim-style, take control of all 32-teams, coach mode fanatic, one who calls plays for the CPU and one who relish in watching the CPU go head-to-head to give these sliders a try.
My sliders won't appeal to everyone, that's understood.

What to expect with these sliders?
Realistic tackling, no skating, ratings matter, realistic stats across the board, competitive games, a thrilling franchise experience and realistic injuries.

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Skill level: All Pro
Game Speed: Slow
League Type: All
Instant Starter: On
Trade Deadline: On
Trade Type: Enable All
Coach Firing: On
Salary Cap: On
Relocation: Disabled
Injury: On
Pre-Existing Injury: On
Practice Squad Stealing: On
Player Progression: Every Four Weeks

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Quarter Length: 15 Minutes
Accelerated Clock: On
Runoff: 15 Seconds

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Fill Roster: OFF
Re-Sign Players: OFF
Progress Players: On (Optional)
Sign Off-season Free Agents: OFF
*If you're taking control of all-32 teams, it's important that you have these all on for each team except the one you're controlling*
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Tutorial Pop-Ups: OFF

Offesive Playbook: Team-Specific
Defensive Playbook: Team-Specific
Auto Flip Defensive Play Call: On
Ball Carrier Special Move: Manual
Auto Strafe: On
Ball Hawk: On
Heat Seeker: On
Switch Assist: OFF

Play Call Style: Slim
Previous Play Information: ON
Franchise Bottom Ticker: Scores-Only
Franchise Gameplan Boost Notification: OFF
Coaching Tips: OFF
Pre-Snap Menu: ON
Player Names: Pre-Snap Only
Camera Toggle: On
Passing Cam: OFF
Offensive Camera: Broadcast
Defensive Camera: Wide
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Volume Control: Optional

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Auto Subs: All 80/60

PLAYER
Quarterback Accuracy - 25
Pass Blocking - 0
WR Catching - 45

Run Blocking - 40
Fumble - 70
Pass Defense - 0

Interception - 50
Pass Coverage - 99
Tackling - 40

CPU
Quarterback Accuracy - 25
Pass Blocking - 0
WR Catching - 60

Run Blocking - 25
Fumble - 70
Pass Defense - 0

Interception - 50
Pass Coverage - 99
Tackling - 75

SPECIAL TEAMS
Field Goal - 50
Field Goal Accuracy - 35
Punt Power - 50
Punt Accuracy - 35
Kickoff Power - 45

GAME OPTIONS
Injuries - 50
Fatigue - 0

Why Fatigue At 0?

To keep the games competitive all four quarters, I've discovered that 0 Fatigue is the best option resulting in accurate CPU stats, ie; tackling, more solo tackles over assists. It's hard to explain this analogy, the CPU's rating drops after a certain amount of plays which slows them down and reduce their performance. Please make no mistake, if you're running a 80 yard TD return or Pick-6 your player will in fact run out of gas and quicker players will catch up to them. Fatigue at 0 doesn't mean your fatigue bar won't decrease when going turbo.

So How Will My Players Substitute?

By using the formation sub for both the controlled team and CPU team. This is a great and better way to rotate the second & third string RBs/LBs/DLs/DBs/OLs. Auto-sub is pretty much obsolete right now. Using this method ensues everyone gets a fair chance at playing, that includes having your 65 overall LB with 95 speed on blitz packages. Something that cannot be done with auto-sub.

Min Player Speed Threshold - 0

PENALTIES
Offside - 80
55 Everything else except for ILLEGAL BLOCK & ROUGHING THE PASSER - 50

XP SLIDER
QB 90
HB 216
TE 140
WR 260
FB 200
T 270
G 300
C 300

DE 120
DT 200
ILB 119
OLB 96
CB 220
FS 160
SS 110

KICK 300
PUNT 300
G 200