I've ended up posting this thought in a few places, and I've realised that it's the same thought in different forms, so I thought I'd spit it out once and be done with it. For the sake of disclosure, I haven't invested in the game, so take this for what it's worth.
The idea of a universal RPG, one that you can 'port any genre into, is very alluring, and I believe it is entirely possible to make a basic framework for an RPG that can work for many genres, but there's one big caveat that I wanted to voice, which is, simply put, that the actual rule system can't and shouldn't be entirely universal. The basic "engine" behind e20 seems to be built around the idea of cinematic action/adventure in a contemporary setting (I'll stay away from the actually very ambiguous term "modern"). Making the basic version contemporary action/adventure is great. It's a good jumping-off point for other genres. However, "contemporary action/adventure" is a genre in and of itself, and genres work a certain way.
Genres are basically made of conventions that audiences and creators alike perceive as sets of expectations. A story that has six-shooters, lots of horses, and it set in the rural US in the late 1800s is probably a "Western," but that's not guaranteed and it's not an entirely rational, categorical determination that makes that decision. We've simply gotten used to those separate and not-by-necessity-connected narrative elements combining into a thing called a "Western." If you flip the gender of the hero, turn a him into a her, you diverge from the Western a little bit. If you replace all the period elements with high-tech but keep the aesthetics--six-gun "blasters" and "robo-steeds"--it's suddenly a cross between Space Opera and Western, but it doesn't actually stop being a Western per se. Genres aren't stable; they merely have somewhat reliable conventions that audiences come to expect and creators use to tell their stories.
The reason I go into all of that background stuff about genres is to come around to the point that many generic conventions mean that the fictional worlds within them function quite differently; that's part of the audience's expectations. In Westerns, a 19th-century six-shooter can miraculously shoot straight enough for the gunslinger protagonist to pop the pips off a playing card from half a ghost-town away. By contrast, in a lot of Space Opera, despite using fabulous weapons of the distant future, nobody can hit the broad-side of a starship. The conventions of the genres vary exactly where the rules of a role-playing game would have to be stable (i.e., the mechanic of hitting or missing your target with a ranged weapon).
Every genre-based RPG brings with it a set of expectations from its players: the expectation that that RPG, by virtue of having the word "Western" or "Space Opera" on the cover, will replicate the conventions of its genre. Therefore, there has to be some degree of variation between the rule set out to play different genres, even if they run off of the same RPG "engine." Otherwise, all the different genres of the RPG will feel basically the same. You can add all kinds of elements other than rules in order to a genre book that differentiate it: setting, flavour, history, cultures, combat opportunities, etc. However, if you don't allow yourself the freedom to change some of the basic rules, then you might miss the most important, but least obvious, conventions of the genre. For example, a Space Opera game is very well suited to traditional HPs--keep subtracting them until you die--but a Cyberpunk game would probably do better with a condition track--keep getting more and more hurt and vulnerable until you die. Two very different game mechanics for two very different genres, despite both being under the general umbrella of "Science Fiction."
Therefore, I cordially recommend (and I've made this plea so many times on the official d20M forum that I can't almost type it from memory) that you start with a base book that's explicitly labelled "for cinematic action/adventure gaming" (or words to that effect), and then with every genre book, you name the genre on the cover, and the first thing in that book is "Here's the rules that have to change in order to replicate a Western/Space-Opera/Wuxia/Superhero game." That way, not only do you achieve the goal of making the game feel like the movies we've all watched and the comics we've all read and the video games we've all played, but you also create for yourself a literal library of alternative and optional rules systems that enrich the variety of the game. Someone who follows the whole line--and I suspect many people will--can pick and choose exactly which rules they want to employ in order to invoke certain conventions in their games. You'll create a gaming audience that knows the rules from the inside out and one that takes part in the on-going debate about those rules. The only tough part is creating modular rule systems that you can slip out and slot in: HPs/condition tracks, Armour as Defence/DR, enhancements on a sliding scale of power/frequency, etc.
My paradoxical advice, for what it's worth, is that if you want to make a truly "universal" RPG, then it can't actually be universal. It has to instead be flexible and multifaceted. It has to understand that going from one genre to another is an act of translation, and all translation loses elements of the old and gains elements of the new. That's the only way it can work, in my humble opinion. A good movie of a book doesn't just shoot the book, scene for scene. It intervenes, it interprets, it makes new decisions based on the form of film versus the form of the prose novel. Peter Jackson knew that and created The Lord of the Rings; Zach Ryan didn't and created Watchmen.
TLDR: universal RGPs can't be 100% "universal" in order to handle different genres. Discuss!