Basically what jDr0id said. I personally prefer the portable versions for various reasons:
-I find them easier to manage and backup.
-I can have multiple versions of the same browser, if the need arises.
-I can easily archive the whole thing before an update, in case that said update breaks anything.
-I like to have everything in one folder, not scattered in 3 locations like the normal installation. Though I have the cache locations for all browsers configured to a ramdisk.

The only minor drawbacks I can think of, are:
-You might need to edit some ini file(s), but those are self explanatory.
-File/URL associations or integration with the desktop will probably not work. I personally have no need for this.
-In case you're using CCleaner, it will not clean the portable browsers, unless you make some custom entries.

Pale Moon has its own portable versions, directly from the developers, not from PortableApps. Opera is somewhat similar, having an option to install it as portable when you run the setup. Maybe newer Firefox versions have the same option?

In the case of Tab Mix Plus, the problem is actually the fault of the developers of Tab Mix Plus who just ignored Firefox Quantum for a year or more while it was in development, perhaps assuming it would just go away, or it would magically provide them with everything they needed without them having to communicate with Mozilla. As a result they did not engage with Mozilla much at all only filing requests for enhancement to Web Extensions for features they needed at the last minute and only asking their users to vote on those bugs also at the last minute when there was no realistic timeframe to expect there to gain momentum on the bugs they filed nor time for Mozilla to consider all of the requests within the already long time planned release date of Quantum.

So while it is very disappointing, sadly it is the fault of the TabMixPlus developers that never engaged and communicated with Mozilla early enough to have a chance of having the features that they needed. Either way, us Tab Mix Plus users end up with the bad end of the stick, but it could have been either prevented entirely or much further along towards a solution now had they reached out to Mozilla earlier. Mozilla gave developers of extensions years of heads-up with their roadmap etc. out in the open, and guidance as to how to proceed in order to ensure compatibility with their future plans and how to engage with them if addons had specific feature requirement needs that were not met yet with WebExtensions.

So I'm more annoyed by TMP than by Mozilla.

A perk of being a systems engineer. :)

Hey not trying to revive this dead thread but this piece of info was too valuable not to share considering the concerns of a few here.

Here it is:

There is now a complete backup of all classic add-ons from the Mozilla Add-On Store, mirrored on the Waterfox CDN. You can use the Classic add-on Archive add-on to view the catalogue. This will be integrated into the next minor Waterfox version (56.3).

Waterfox Blog - 56.2.4 update

Hey, I do not mind that but :D

Oh pardon me good sir! :O