To be fair, the Mamiya RB/RZ are pretty freakin' big and unwieldy. Granted, with MF you often aren't swinging it around like you do with a 35mm format camera, but from the pics I've seen the 6x4.5 format cameras are much handier and easier to shoot with not from a tripod.
Much of a muchness, I think, depends if you're used to Waist Level Finders or Viewfinders, and what you shoot. I started on (d)SLRs, but like I said, I'm getting more and more used to WLF, for full-body portraits and street it's just easier. Headshots handheld the level-prism of the Mamiya is better. I got TTL metering prisms with all my MF gear to begin with, because I was used to my 3 & 7D, but the freedom of WLF and my external meter is very liberating.
I've just compared my MF cameras, the Mamiya 645AF is actually bigger than my 6x6 Hasselbladski (Kiev 88CM). The body is shorter (because of the smaller mirror and shorter flange-distance), but then the viewfinder sticks out further. The Mamiya is wider because of the grip, the Hasselbladski is more cubic. Height-wise the Mamiya's prism is smaller (because it's integrated probably helps), but only by 1cm, and that's comparing the Hasselbladski's 45-degree prism (the level prism is smaller I think, but I don't have one, and with the WLF it's shorter than the Mamiya).
Ironically, given my usage, last big shoot I did with the Mamiya was down the Great Ocean Road to Melbourne and back with a 45mm. 645 for me is landscapes (and conserving film 500km from the nearest shop that sells 120), and landscapes go on a tripod, but as I discovered, viewfinder on a tripod is rather unwieldy, give me Live-View or WLF any day. 6x6 is my street and waist-level full-body portrait machine, it just works better handheld for me.
So yeah, you're right, but the other way. It's not that 6x6 is easier on a tripod, it's that the 645 sucks on a tripod (at least for me, YMMV)
But yes, RB/RZ are bigger, I've never held one but I've seen them in shops, it's a whole world again up from the Hasselbladski size. Partly comes from the bellows focussing, partly from the larger mirror, partly from just the build quality (ever seen a 7D next to a 1000D?). But I know some people who shoot street with them, I've seen a GF680 used handheld, and hell, I've heard from a guy who shoots street with a Speed Graphic.
Anyway, just for a size comparison, here's some shots with standard lenses. Mamiya 645AF with Volna-3 80/2.8 (I don't have a Mamiya 80mm), Kiev 88CM with 45degree TTL-Spot prism and Vega-12 90/2.8, Pentacon Six with Kiev-TTL meter and Zeiss Biometar 80/2.8, Kiev 60 with Zeiss Biometar 120/2.8, and Eos 3 with Nifty Fifty. I don't feel any of them are more unwieldy than my 3 / 7D, once I put a zoom onto the Canons they're bigger than the MF.