I'd like to see one that was very realistic vs NFL standards.
16-32 team, IDP, 45 man rosters
Salary Cap
Snake 7 Round Rookie Draft
Franchise Tag
Escalating signings - Feel like you should be able to resign a player before they become a UFA. But you need to pay the massive premium for them. Some form of tiered salary system here would work, if they just finished say #1 should be it's own tier, Top 10 at their position another and so on. So if you can make the cap room work and sign them to a new longer deal then you should be able too.
Auction FA Draft - Similar to the NFL. Everyone gets to bid one the FA's available.
Practice Squad - 1-2 slots, players to stash... cannot be activated mid-season. Does not use up contract time. And can't be a pro for more than... 2 seasons? So essentially, this would be for guys like say Blake Bortles or Donte Moncrief. Someone to stash and not harm your roster slots and not harm their contracts. But if they happen to blow up a lot sooner than you thought, you'd screwed and have to watch them make tons of points on your bench. Also something where another team can offer them more than their contract, say double? And you can either match it or let them go? So say you have Bortles on a $6/5 year contract on your Practice Squad. If someone wants they can offer him $12/5 year contract and take him from you if you don't wanna match it. Think this would add a lot of interesting interactions to the league.
Starting Lineup - QB, RB, WR, WR, RB/WR, WR/TE,TE, K, DE, DE, DT, DT/LB, LB, LB, LB, CB, CB, S, S, CB/S - You should be forced to start legitimate styled teams. You can run a 4-3 defense if you want, a 3-4 if you want, base 3 Wide Set, or a 2 wide Iso Set, 2 TE set etc. Obviously scoring would have to be worked out a little to provide some level of incentive for actually running a 4-3 instead of a 3-4 base.
So yeah, I'd love to see something with these kinds of rules. If I had the time I'd try to setup and commish a league like this but I simply don't have that type of time on my hands.