From 2013:
kamnet wrote:Having recently started to participate in the Reddit OpenTTD community, I've found that even more new players there ask the question about best/must-have mods than the do here. So, I took some time to make my suggestions, which I'm copying here.
Nearly four years have passed since my original posts on this topic. In that time, there's not a lot that has changed. But what has changed is that I took up Planetmaker's suggestion and began to curate the OpenTTD wiki's NewGRF List, providing helpful categorization of NewGRFs and links to their discussion so you can better evaluate them before downloading. I won't claim it's complete, but it's fairly comprehensive. Feel free to help curate it along with me.
With that said, I will update my 2013 post below with a few updates of additions and changes since that time.
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I wouldn't say that there are any "must have" modifications. Plain OpenTTD by itself is very robust.
Although if there is a "must have" at this point, I would skip the stable version 1.3.2 and download a nightly instead, which has introduced the new Cargo Distribution (cargodist) patch. It radically improves distribution of passengers, mail and goods. It will move into stable OpenTTD probably in the 1.4.x version. But, still, good play can be had (and has been had since 2006) with the non-CD version.
The above is now struck out because the CargoDist patch is now part of OpenTTD's core source code, and it is MARVELOUS. It should be enabled for all game play, in my opinion. If you want an early look at what could be the future, however, look into obtaining a forked version of OpenTTD that includes NotRoadTypes, which brings up to 15 slots to add to both road and tram infrastructure east. So far new sets have used that to provide different graphics to roads, and some have experimented with adding separate trolley bus and trolley trucks.
Most NewGRFs have no problem operating with each other, and typically the few that do not expressly note which ones don't work with each other, if not going out of their way to disable themselves automatically. The only major issue you might have is that NewGRFs of the same type aren't balanced against each other (and this still remains the case in 2017). For example, trains from one set might be insanely expensive compared to trains from another site. Newer versions of NewGRFs are starting to provide options for better balancing, either through auto-detecting other sets or allowing you to modify the costs via parameter settings.
Here's my rundown for most popular NewGRFs.
INDUSTRY: FIRS has pretty much become the dominant industry set, due to frequent updates and tweaks from Andythenorth. ECS Vectors and PikkaBird Industries (PBI) are still good, but haven't had any updates or changes, save for George updating ECS' graphics with Andy's FIRS/TTD-style graphics. FIRS has spawned some children though, such as AuzInd and Stockpile Industries (SPI). OpenGFX+ Industries is also still there providing a step up from the default industries.
PLANES: The most popular is Aviators Plane Set (AV8), second would be the never-finished-always-updating World Airliners Set (WAS). Both are compatible with all available industry sets. There's a few other small sets out there as well, some of them are eyecandy, but some are good improvements such as VACE which provides VTOLs.
SHIPS: There hasn't been much change here. SQUID Ate FISH (aka FISH 2, the successor to FISH) has become the dominant set, in my opinion. FISH 1 continues to remain popular, and it's spawned at least one child, RedFISH, which has improved specs suitable for playing on Reddit OpenTTD servers. NewShips updated with newer graphics and improved specs, Sailing Ships still give you great gameplay for the 18th and 19th centuries, WSF provides you a nice set of ferries for passenger transport.
TRAINS: 2CC TrainsInNML is successor to 2CC Trains of the World, it still does the same thing but it's even bigger and better. To help bolster it, you now have add-ons such as 2CC WagonsInNML for better cargo transport. NARS 2 has gotten an update, and NARS 2 Add-On Set provides even more North American-style trains and wagons. UK Renewal Set 2 (UKRS2) still exists and plugs along, as does OpenGFX+ Trains. Newcomers include Iron Horse (from Andythenorth, author of FIRS & FISH) and the companion Termite rail set, and also AuzTrains. Japan Trains has updated, and there are now loads from regional train sets from South America, UK, Europe and Russia, spread across various sets.
ROAD VEHICLES: eGRVTS is probably the most popular set. For more variety, check out HEQS and George's Long Vehicles. Lots of smaller sets as well, and some regional variety sets. There's also an OpenGFX+ Road Vehicles set that improves the default vehicles, including adding ECS & FIRS compatibility (thus you don't need to download ECS & FIRS Original Vehicles). Road Hog from Andythenorth is a nice improvement in the area of generic but realistic-style vehicles. There are now sets dedicated to improving buses from North America, South America, Europe and Asia.
TRAMS: Much improved from four years ago is the number and variety of trams/streetcars. I am unabashed in pushing 2CC Trams, a set that I helped to conceive but do admit is not quite complete, so play at your own risk. 
There are many other tram sets that all do a wonderful job, so I won't try to compare them but instead I say play with absolutely all of them! HEQS (again, Andy) is a particular stand out because it provides exclusively industrial trams, and Road Hog is a nice step-up from that as well. For a bit of a change, try playing with Streetcars instead (which replaces overhead tram catenary with streeetcar/trolley car wires), or maybe even the Urban Suburban Monorail set, which replaces trams with a Wuppertal-style overhead/hanging monorail.
AIRPORTS: Right now I'd only suggest OpenGFX+ Airports, which improves the default airports by adding 4-direction rotation. However, skip the outdated stable version on BaNaNaS and grab a nightly version from the OpenTTD developer repository. The nightly version has several new airport styles for airships/Zeppelins/blimps/balloons, helicopters, more dirt runway airports, and improved small airports. There are a few other ancient sets which simply change the style of graphics, but because of changes in OpenTTD code, they're glitchy and/or broken, and don't have anybody to take care of them.
STATIONS: I can't really suggest one is any more popular than the other. Most station sets are designed around a region (Canadian Stations, Dutch Stations, British Stations, etc.). Industrial Station Renewal, the older Industrial Stations, and DWE Industry station sets all are focused on industrial themes. CHIPS and VAST are fairly popular as well. Other than the addition of Australian Stations and the update to Japan Set Stations and Dutch Stations, there's not been a lot of work here in the last four years.
BUILDING SETS: It was pointed out that I previously neglected theses. There's quite a few, and some styles of sets can look nice together, others not so much. Pretty much Total Town Replacement Set is the king, having aged well over the years and one of the oldest sets around. Japan Set Buildings are also popular. The former North American City Set/Canadian Cities Set is no longer available for download, quite a blow to the community, but you can still find its predecessor, North American Building Set, which brings some architectural cool to the early- to mid-1900s. There are several sets based on European countries (UK Town Set, Swedish Houses, Polish Building Set, etc.). You should probably only pick one set, but you don't really know until you try them all.
OBJECTS: Here is where a lot of effort has been directed over the last few years. Objects don't change how the game is played, it just makes stuff look prettier and cooler. There's way too many to try to sort by popularity, and again I say play with them all, if you can! You may very well never actually get around to using most of them because they're just so cool. But if you don't know what the possibilities look like, I suggest you check out the Screenshots threads and be prepared to be blown away. 
32bpp/Full Zoom NewGRFS: This is another significant change from 2013. OpenTTD now implements 32bpp graphics and up to 4x zoom-in level, which allows for graphics to be drawn in a more detailed (but slightly distorted) manner. They're all quite popular with those who feel that the traditional 8bpp graphics look tired, outdated or just not good. I don't feel that there is one that is any more popular than the others simply because there are too few of them that really compete with each other, most of them are great complements to each other. While the file downloads can be HUGE (many hundreds of megabytes), I do suggest you try downloading some and seeing for yourself. The visuals can be quite stunning.
With the exception of industry changes, none of these NewGRFs give you any sort of significant improvement other than visual and aesthetics. They're all just a change of pace from the vanilla. The REAL game changers come with competitive AI players (none I'd recommend over the other) and GameScripts, which give you new goals and challenges (again, none I'd recommend over others). Any single one of these will get you to up your game a bit, and almost all of them can be mixed and matched to get a really complex and competitive game. Or, you could go the opposite way and find AIs that serve exclusive tasks (like servicing only mail, only passengers trains, only airlines, only buses) and build your own cooperative game.
