It depends on the situation. I've seen deer hunters miss a perfect shot because they had a new rifle with a slightly different safety. But that was not life-threatening.
A friend on a SWAT team used to laugh about a buddy without any military experience who was a dead shot with his MP-5. When they transitioned to M4's, he took weeks to re-learn a simple mag change. And still sometimes bobbled it for a LONG time afterwards. I've heard stories of the reverse as well; folks who knew M-16s like a part of their body and cursed the MP-5 when the bolt didn't stay open and they had to lock the bolt open BEFORE inserting a new mag.
I limit my platforms for serious use. Either an AR-style or the FN-FAL. They are different enough and I have enough hands-on time with them that I can do mag changes and all other operations automatically with either. Same for the 1911 or CZ-75. I used to hunt with the Savage 99, but I'll probably retire it in favor of my 6.5 Grendel AR.