I get this question a lot, so I decided to setup this page for it.
This is often a topic for debate: which issue is better than the other.
Functional differences
ZX Spectrum 48K issue 2 boards require manual trimming of some video output parts.
To do this properly, an oscilloscope is required.
Even with perfect calibration, the picture is often not as bright as with an issue 3 or up board.
From issue 3 upwards, IMHO all boards are about equal when it comes to functions.
Having repaired every board issue, I do not have a clear sign that one has more issues or develop faults sooner than the other.
ULA type
However, it is known that ULA 6C001E-6 types, get hotter than the 6C001E-7.
Though I add a heatsink to the ULA chip (properly, with thermal paste), it could be that the 6C001E-7 will last longer, hard to tell.
I have not heard anyone have a faulty ULA 6C001E-6 though that has a heatsink on it, so maybe the heatsink will avoid that chip to fail because of heat quite well.
6C001E-6 ULAs are on issue 4A boards and upwards.
Find more info about the ULA chip here: https://www.bytedelight.com/?page_id=2678
PCF1306/ZX8401 chip
Issue 6A boards have a PCF1306/ZX8401 chip instead of 6 discrete (74LSxx) chips.
That PCF1306/ZX8401 chip was developed for the ZX Spectrum toastrack (128K) model, but was also used for the last batches of ZX Spectrum 48K.
Common problems with about any board issue
Many ZX Spectrum 48K boards have transistors at the video circuit, that blur the output a bit.
If I notice this, I replace them with the proper transistor type.
I nowadays (2022) replace the small capacitors at the lower 4116 memory chips, since this tends to remove vertical bars (‘jailbars’).
Of course with my refurbishment work, I replace all electrolytic capacitors, with only axial Vishay capacitors, the best looking and best quality ones.