Floor Stander or Monitor w/ 2 subs? What does the later give up in a large room?

They are a bit pricey and rarely do they come out on the used market, but if you can afford them Silverline 17's are superb.

Well smaller monitors plus separate subs gives you greater ease and flexibility for setup compared to two large heavy full range floorstanders but be sure still the room will accommodate that as well.  
If you want to be able to optimize with fewest constraints a dedicated room if possible is best. 

@newbee 

The SR-17's are legendary and hard to come by.  Even with those, will they fill out the soundstage with full size figures?

@mapman  Yep. It does come down to that. I must kick myself for NOT doing the room when there was opportunity. Oh well. I was  a builder. It might be cheaper to build addition than to find a small speaker which will compete with the speakers I now have. Then too, that material is not cheap either.

Ok ok, I’m sorry... My opinion is that a pair of Monitors with a pair of subs should kick butt! I’d suggest getting monitors that play low because Rels are more of a sub bass system... you may have a hole in your freq. response if your monitors don’t play low.  I have a REL S3 snd this is what I am experiencing.  I put another sub in to fill the 40-80hz range that my Totem Arros were lacking in (dynamically).

I hadn’t heard of watkins gen 4 speakers before but they look nice.  You may want to take a quick look at Salk Speakers.  They use high quality drivers as well and look stunning.  Your wife would love the aesthetics! 

I think you could have a fantastic sounding set-up with some monitors and a pair of S5’s but I DON’T think you’ll be getting the midbass thump / smack in the chest type of dynamics that something like a Tekton Double Impact would offer up, obviously.

I think you’d be better off trying to go for a 6.5” midbass driver or larger, in order to try to move more air in that large listening space, but if you already heard the Watkins and like them, go for it!

If you didn’t buy the S5 yet, my local magnolia has an S5 SHO for $1250...

Thanks @b_limo . Yes the Watkins are pretty good. I've heard them and was shocked at how deep they go and the natural sound they exhibit. I think you have some valid & good ideas. And $1250 for the S% is a steal. Mine are actually Sumiko S-10's which seem to be a clone of the S-5. It has the same specs but different cone material. (Fiberglass) Plus the Neutrik connector. They integrate  very well just like the Rel. I've had Rel before and just happened to run into these. I love what they do with the whole sound not just more bottom end but the mains sound much bigger. They are discontinued now. I suspect Rel would have sued them if they kept producing them. But Sumiko was the USA Rel distributor for many years