@Thenomain mentioned in a different thread we maybe should look at aspects of the nWoD and see what needs (or could benefit from) adjusting for MU*. That makes sense, so why don't we discuss that a bit here?
I'll submit some of the things off the top of my head. That's by no means a definitive list so feel free to shoot them down and introduce your own - all I'm asking is that we try to organize our observations on mechanics a bit, just to avoid long rants which are hard to comment on. You can use my format for that or your own, whichever, as long as there's some logic to it.
So here are some initial thoughts.
Resource management
Reasoning: Characters on MU* are often played daily, for months/years. It's tedious and repetitive, causing some players to not want to deal with it as an in-game mechanic. Implementations in the past have been iffy either due to the introduction of micromanagement ('my vampire is starving? just because I forgot to type +hunt it doesn't mean he forgot to eat!') or because they made it resources irrelevant by not ever running out.
Proposal:: Limit resource management to allowing characters to set it manually. Keep them as thematic elements but only keep track of them on a per-scene basis starting from the maximum per power trait, unless explicitly set by the players lower. Assume otherwise the characters are IC replenishing their supply during downtime.
Powers and effects over timeframes and locations
Reasoning: On table-top time can be handwaved very easily. On MU* - especially in Vampire - that's not the case since it's a shared setting; for example if a character falls to torpor for a year they might as well be killed. Similarly a power which exiles a character or group from a city is a blow in table-top but it marks the end of the PC on a MU*.
Proposal: Place penalties or limit the duration of such effects as appropriate. Reduce torpor to a matter of days (or offer thematic alternatives to awaken a slumbering PC), induce penalties for staying rather than forcing the PCs out altogether.
Telenuke
Reasoning: Oh, the beloved telenuke. On table-top it's a tool for the PCs, as it'd be a complete jerk of a ST who kills a character who can't fight back. On a MU* it's bad because it's been often used as a way to treat PKs with no way of fighting back and, worse, no way of even at least milking one's death scene for some roleplay.
Proposal: Limit it to NPC targets. For PCs it can cause damage, trauma etc but it shouldn't lead to outright character demise.
Arcane XP/Renown/etc
Reasoning: On a table-top game the Storyteller is always present so that 'special' roleplay happens constantly by definition, yet that's not the same on MU*. Players often have to resort to petition for custom-made scenes just to justify expenditures, leading to pre-scripted scenes no one present enjoys, or to plot starvation in the absence of people running PrPs.
Proposal: Allow IC justifications for the 'special' stats. Offer incentives to players who do go through the trouble of accumulating on-grid justifications to reward the behavior through extra XP.
That's what I had in mind to begin with. Feel free to add your own or shoot these down, whatever.