Starting the early 1980s I purchased a number of systems coming out that promoted themselves as being able to handle multiple genres. They generally fell into two categories: systems that used a core set of rules but sold each product as a separate RPG, and systems where the core rulebooks were genre-neutral and the additional books supplied specific rules for different genres and settings.
The former – separate RPGs that shared a set of core rules – was how the Basic Roleplaying family of RPGs was sold by Chaoisum. I owned Runequest 2 and Call of Cthulhu. Once you had learned how one worked the other was very easy to learn. Another notable game using this approach at first was the HERO System.
Then there were the games where the core rulebooks were genre neutral with separate genre and setting supplements. GURPS was first game I encountered – that was in 1987 – taking this approach. Then later on the aforementioned HERO System switched to this approach as well with its 4th edition, although in the case of Champions they still had a standalone superhero RPG.
There are other systems designed to handle multiple genres with a core set of rules, however Basic Roleplaying, HERO System, and GURPS are the only ones that I have personal experience with and which focus on what you describe as simulation.
Of these three, I consider GURPS the best. I feel that books in all their editions are well written, well designed, and well researched. I been playing GURPS in a number of campaigns since 1987. While the vast majority of my campaign take place in the fantasy genre, GURPS made it extremely easy to add additional mechanics and subsystem to handle the different ideas I came up with over the years.
- Incorporating the free-form White Wolf magic system from GURPS Mage the Ascension as a higher form of magic than the system outlined GURPS Magic.
- Using the details of early black powder weapons in GURPS Low Tech as the foundation for one fantasy campaign where the players stopped a rebellion by a rebel baron who discovered how to create black powder and bronze cannons.
- Incorporated GURPS Martial Arts to give the fighting styles of fighters from off-map campaign areas an exotic feel.
- Used GURPS Psionics to create an exotic form of magic for another campaign.
Also in recent years with the rising popularity of the Dresden Files, steampunk, and other mixed genres, Steve Jackson Games have issued a number of supplements to handle those genres, like GURPS Monster Hunters. You can mix and match, combining GURPS Action with Monster Hunters to create something like, say, Speed or Die Hard but with magic and/or monsters.
GURPS also allows you to vary the level of simulation by giving you options as to how much detail you want to incorporate. You can easily use or not use miniatures for combat. Combat can resolve with a three rolls (attack, defense, damage) with a few modifiers, or you can incorporate miniatures, detailed maneuvers, and use the full range of modifiers.
GURPS also covers the roleplaying side with a number of notes in various genres books on how to set up NPCs and different types of campaigns. They also used their e23 PDF store to release specialty products that might otherwise not be viable in print. For example, GURPS Social Engineering, which covers various types of social interaction and relationships in fine detail. Or GURPS Underground Adventures, which covers both real-world geology and fantasy geology as found in comic books or pulp fiction.
GURPS' main weakness isn't complexity, but rather the fact that it is a toolkit and requires some work, before starting a campaign, to decide what options you will be using. This is one reason why I have largely stuck to one genre in my twenty years of running the system. I have copious notes and aides that I created which save a lot of work anytime I start up a new fantasy campaign, but if my interests were different at the time, I could have easily had the same thing for Urban Fantasy, Cyberpunk with magic, or any other mashup you can think of.
I like GURPS over the HERO System because the heart of HERO System is the (super)power system. While excellent for many things, it kind of gets in the way when you have to use it to represent every game-mechanical effect. While GURPS 4th edition has a power subsystem of its own, it's only one among numerous subsystem of varying complexity, so using the power system is not the only option as it is in the HERO System.
Chaosium now has a core rulebook for Basic Roleplaying that I own, however I find that it still show its legacy of being a core system for distinct RPGs. That is, it's hard to truly mix different subsystems in the way that GURPS allows.
The core of the system is found in GURPS Lite, which is a playable subset of the full GURPS rules.