Last night I had an issue with TCP Optimizer 4.0.4 (which was just recently released) apparently conflicting with Avast Internet Security 11.1.2253. This is on a Windows 7 Home Premium SP1 (64-bit), 8G RAM desktop PC.
As soon as I ran TCP Optimizer, selected “Optimal” and clicked on “Apply changes”, all Internet access became slow … molasses in snow flows faster than that! 
Both Firefox 45.0 (browser) and Thunderbird 38.6 (a mail client) could barely fetch content (Thunderbird: not getting far enough to know it has to ask me for the master password; Firefox, taking tens of minutes just to load a very simple web page) and I ended up aborting both programs after a few minutes.
Non-Internet tasks ran at normal speed. A virus scan (“Smart Scan”) was clean.
Telling Firefox to “refresh Firefox” (in Help → Debugging Information → the “Refresh Firebox” button) didn’t help, but it obviously refreshed the Firefox settings.
A “repair” (“Uninstall a Program” → “Avast Internet Security” → “Change” → “Repair”) with its following reboot didn’t change anything.
And of course there were multiple reboots of the Windows box (not just the prompted reboots from TCP Optimizer telling me that some settings require a reboot to become effective, or “Uninstall a Program” → “Avast Internet Security” → “Change” → “Repair” prompted me to do), three reboots of the “gateway” (the combined modem/router I am renting from Comcast), reseating both ends of the Ethernet cable and the coax cable to the “gateway”.
I ended up rerunning TCP Optimizer choosing “Windows Default” and rebooting, and then my Internet access was suddenly quite fast, both in page loads in Firefox and in connecting to the mail servers and downloading new messages in Thunderbird.
Later that night I ran a full system scan and, again, Avast! didn’t find anything amiss.
My suspicion is that there might be a conflict between Avast Internet Security and one or more settings that TCP Optimizer makes when TCP Optimizer is told to set “Optimal” settings.
What I haven’t had time to try yet is going back and selecting “Optimal” to see if this again causes problems, or selecting “Optimal” but overriding the “Host resolution priority” settings back to the Windows default values. If I have time, I may give that a try.
Or is it the general informed opinion that maybe modern operating systems have progressed to where such tweaking is probably obsolete except in niche circumstances?
TCP Optimizer (TCPOptimizer.exe) 4.0.4 can be found here: http://www.speedguide.net/downloads.php
Thank you for whatever insight you can provide, even if it is to tell me I can now stop going overboard in pursuing diminishing returns. 