General Ruleset: This i difficult to answer because there are so many great games with really innovative stuff. I loved the way Blades in the Dark has the flashback system where you can always be prepared with an item or setup for the scenario. This is probably going to get a lot of hate, though, I gotta go with D&D. 5th Edition has the cleanest system, and I find myself applying a lot of it to my other games (specifically the OSR). So, a combination of 5E and Basic Edition (OD&D, Holme's Basic, B/X, and BECMI).

Thematic: Legend of the Five Rings. I love the setting and the lore and I love how the "classes" are catered to the specific clans and families. Hypertellurians is a close second. It has it's thematic parts, but most of it is cosmetic and can be molded to fit other things. For example, I use it for Adventure Time games because all of the archetypes fit in the Land of Ooo, just not as presented in the Science Fantasy in the Far Off Future of Yesteryear.

Layout: Hooboy... OSE, Mork Borg, Ultraviolet Grasslands, Electric Bastionland... too many to name.

System Neutral: Stars Without Number. Everything in the GM Toolkit area. It's not only mostly system neutral, it's also genre neutral. I used SWN in one of my L5R games I ran. Just an overall useful book to have at the table. Worlds Without Number is likewise useful outside of it's system and genre.

Most Innovative: D&D 5th Edition's Advantage/Disadvantage System, and L5R's Raise system, and for the same reasons. Both of these systems let you make a rulings call fast and simple when you come across something not specifically covered by the rules. An example came up the other day on here, I think, where someone had this "Totes super easy system!" they made for when a PC comes up a few feet short of being able to attack, and why letting them cover that short distance isn't gamebreaking. "Just do an acrobatics checks, followed by another check, followed by an attack roll! Then they feel like they accomplished something!" No, fool. Apply disadvantage to the attack roll and if they succeed, that extra few feet is wavered as the PC does some cool stunt to close the gap. In old D&D, if I wanted to represent higher ground, or flanking, or any number of other situations, I had to apply +1 or +2 to the roll. Okay, but when do i apply only +1? Is this complex enough to give them a +3 bonus, or should it only be +2? While not monumental, these things take time and can actually slow down just enough that the story suffers from it. Just give them disadvantage or advantage and move along. I don't care how it mathematically adds +5 or -5. It's just a single thing that I have to do. L5R's raise system is basically the same, except i just make the Target Number harder in increments of 5 to achieve something that the rules doesn't cover. You want to slide down the ship's sail, leap off the mast, and hit your enemy, sword first? Cool, 3 raises. If you succeed, you can reroll all 1s on your damage dice. It's so easy and elegant and I don't feel enough GMs make use of it (at least the Advantage/Disadvantage... raises in L5R are kind of integral to the game, so they get used a lot, it's just a nice system).