the main problem I'm aware of is that systems with no bios and mandatory carts cannot be launched when you start "mess.exe" only
I cannot really remember other big issues with the internal UI that are not fixable regressions (even if my memory could be doing a bad job
concerning the OP report the situation is tricky and it probably needs someone with a better understanding of how options from ini/cmdline work in MAME
the culprit is in src/emu/mame.c lines 233-234 which sets ramsize to "" with command line priority (which is higher than ini priority)
however, we cannot just drop those lines because they are there for one specific reason: if you launch from commandline e.g. "mess macclas2 -ramsize 6M", and then you switch to maciici from the internal UI, then without those lines the 6M option would be fed to maciici which would find it invalid (emulator could even possibly fail in this case if you switch to a system with no -ram option, but I haven't tested...)
those lines currently 'unset' the invalid option, but unfortunately prevent the ini value from being used... and I have no idea how to workaround this procedure without breaking some other case
what makes really unfortunate the situation is that RAM options cannot be selected from the internal UI (and it resisted to all my attempts to add support for it, because of the way the ram device is designed), so that users are forced to specify ramsizes at command line for the time being...