My brain is rusty, but I feel like MSDOS 5.11 was where things finally just worked. TSRs, memory managers, etc. Moving a lot and not being a packrat I've lost some of that history. It'd be interesting to see 5.x and 6.x released.
I think it was 3.3x where things started working. I don't recall 4.x being around much. I do remember 5 and 6. For some reason 4 never made a splash in my circle of friends.
It took more base memory than ever. It had a complicated code page system that most people didn't want, and a clunky early version of IBM DOSShell that was scorned although it grew into something useful.
But it supported disk partitions over 32MB, and for that reason, it was reluctantly adopted. If you had a 286 or 386, then there were measures that you could take with a memory manager to make it not so bad, but on 8088/8086 class hardware, it didn't leave enough free memory for many big apps to run.