I seem to have stumbled over an issue related to the "Interrupt Speech with Any Key" option. The diagnosis is not exactly scientific, but after a bit of evidence gathering, I feel like this option is to blame for a very sporadic (and somewhat maddening) issue I've experienced with HS + LEDBlinky.
I believe I am using the latest HS and LEDBlinky on Windows 10, with the former from 2015, IIRC and the latter downloaded a few months ago from your site. My HS setup is as simple as possible, at least WRT MAME and RA, which make up the bulk of my "wheels". No HyperLaunch; it gets stuck in memory, unless force-closing MAME and RA in CloseProcess, which loses high scores. So that thing was out from the start.
I looked into RocketLauncher at the beginning and realized it was just piling on more complications to the HyperLaunch failure (and was apparently written by the same people that wrote HyperLaunch), so skipped that as well. HS just launches MAME and RA and when they exit, HS regains the focus and all is well. That has always worked for me 100%, which is the standard I was after. No special pause screens and no "fades", but who needs the latter when MAME and RA launch almost instantly?
I also skipped Joy2Key, XPadder, etc. No need for those, as I just mapped the keys and gamepad buttons in the same way for RA and MAME (and various others). The only add-on I am using for HS is the oddly-named "Startup Script", which is great for gamepad input (HS sucks at that too) and its roulette function that spins to a random game.
Anyway, I have two machines: one is for development, where I tested the setup to death for months, launching hundreds, if not thousands of games *without* LEDBlinky. The other is in a cabinet and I tested it thoroughly with identical results, using the same exact files that run on the development box. I just copied the containing folder over to the cabinet and started launching games. Wonderful. Then I added LEDBlinky to the mix.
After spending a few weeks fiddling around, I managed to get LEDBlinky doing what I wanted without issue and never had any issues launching games during this time; but at some point, I turned on this "Interrupt Speech with Any Key" option and, not long after, began experiencing sporadic "silent" failures, where everything worked, except no games were launched.
When this happens, the HS log looks the same as always (of course), LEDBlinky announces the game and controls, lights the correct buttons, etc. But HS never even loses the focus, failing to launch anything. I could shut down HS, check Task Manager for anything stuck (nothing ever there), restart HS and it would *still* persist in this inane behavior. Then again, on occasion, it would somehow snap out of it after a restart and start launching games again.
As I was testing this (and tearing my hair out), I focused on the initial announcement of the HS controls and remembered that I had turned on that Interrupt option to be able to skip it. So I turned it off on the next failure to launch, re-ran HS and all was well. I left it off for a while, re-testing dozens of times and never an issue. Then I turned it back on at some point and the issue came back. So I turned it off again and was immediately able to launch games again.
I realize that the interaction between HS and LEDBlinky is hard to debug (e.g. HS fails silently), particularly without the source code for each, but based on the evidence gathered so far, it certainly seems like this Interrupt option sometimes causes this mind-boggling failure on the HS end. I can only speculate why and have not been able to think of a reason that this option should cause such a problem.
As mentioned, it was always sporadic, as I was often able to "cure" it by restarting HS a few times. Possibly it is the timing of the speech interruption that leaves HS in a bad state? Just to note, I did see this happen to the odd systems that use HyperLaunch as well (e.g. Daphne).
BTW, love the Pixelcade integration. Just added that and while testing, I noticed that I somehow had that Interrupt option checked on again, after marveling at the light shows in the menus, hitting the "Enter" button and then seeing no game launch. Turned it off and games immediately started launching again. Seems like a pattern at this point.
So that option is now turned off *forever*. Kind of sucks having to sit through the HS instructions in full on each launch (though I've found they get interrupted anyway in some cases), but I'll take it, as long as the games launch as expected afterward.
Anyway, just wanted to note this, though it will be buried in this single thread of a forum, perhaps others going through the same thing will be able to dig it up through Google. The most maddening thing about it is that everything else works perfectly and then it completely fails at its primary (and simplest) task, which is launching games.
As mentioned, I can't assign blame here, but seeing what a miserable excuse for a Windows app HS is, with its many documented (and often inexplicable) problems, I'll chalk it up to another mystery on its end. Despite its various quirks, I am still a big fan of LEDBlinky.

So, has anyone else seen such a problem with HS + LEDBlinky? I Googled for a while, but it's impossible to find specific reports of this nature, due to all of the decade's worth of reported problems and confusion out there WRT HS. As mentioned, having one long thread for LEDBlinky conversations isn't helping either.
One more clue: when it works, it always works (i.e. if the first game launches after a HS restart, all games will launch, at least until the next restart) and when it fails, all games fail to launch, at least until the next restart. That's part of what made me focus on the timing of the startup sequence, announcements, interruption, etc.
Will post back if I find this problem happening again *without* that Interrupt option checked, but I am hopeful that won't happen. At this point, my gut (and the evidence so far) tells me that turning off that option is indeed the "fix" for this issue. I sure hope so, as the next step would likely be to find another front-end (and learn to work around a whole new set of problems, I'm sure) or to live with a system that should work perfectly every time, but sporadically falls flat on its face for seemingly no reason.

Thanks in advance for any clues, no matter how seemingly insignificant, and Happy Holidays to all!
EDIT: So the checkbox may be a red herring, though I'm still somewhat convinced that this has something to do with the integration of LEDBlinky and HS. But turns out the checkbox in question is a bit of a weird interface and it threw me off. Turning it off without selecting a key in an adjacent control doesn't do anything, which can be seen by restarting LEDBlinky (the Any Key checkbox will be checked again). Still, opening and closing LEDBlinky seemed to cure it each time. I just restarted HS numerous times without this weird launch issue, so could just be another strange (and sporadic) HS problem after all.
EDIT: Typically, when UIs do odd things, it is a good spot to ignore what the UI is doing and refer to their settings file, Settings.ini in this case:
AbortSpeechAnyKey=0
What does that mean? Don't abort speech with any key? It looks like it could represent a Boolean value, but IIRC, selecting a key in the UI changes that value to a key code. I'll have to look at that again, as maybe that checkbox does change the value to 0 on un-checking it, but incorrectly displays it as checked on restarting the configuration app. Or perhaps somebody can chime in with what this value means to the app.

So maybe it wasn't a red herring. Will check on that...
EDIT: So the 0 does appear to be represented by an unchecked box in the UI. That makes sense and presumably it is a 1 if checked. I may have forgotten to hit Save at some point, but I am not sure how that box ever gets checked again (which it seems to have done earlier), as I never touched it. Perhaps the key is a different value that is only referenced if Any Key is turned off. I did change some other settings and hit Save for sure, but I never wanted to see that box checked again.