Great topic David1! Thanks for posing the question. I'm enjoying reading and seeing photos of everyones responses so far. Lots of great ideas and suggestions by everyone! Here are some photos of mixing semi - scale and scale from my layout. Click on photos at bottom of this post for captions with explanations.
When I first got back into the hobby 15 years ago my intension was to stay with my old 027 track and switches which I still had packed away, along with my Lionel locos and rolling stock, from when I was a kid. This intension was based on my experience in checking out train stores and hobby shops, reading OGR and CTT, going to local train shows, etc., about 16 and a half years ago .... and WOW was I surprised at how much the hobby had evolved ( just as many of us have experienced ) and WOW was I surprised at the prices of toy & model trains!!! My thought at the time was; this is a rich persons hobby and I am not a rich person ( at least monetarily ) so I'll be happy to stick with my toy trains from when I was a kid. Well .... the rest is history as they say.
I now run mostly scale engines and rolling stock both freight and passenger. Because of my layout's size I don't have enough room to turn scale articulated steamers so I do run a MTH RK Y6b mallet with scale 50 ton hoppers, semi scale gons and flat cars, and the look is fine ( at least to my eyes and the eyes of the vast majority of my visitors ) When I run the Y6b I usually simultaneously run my Williams by Bachman scale GE 44 tonner on the adjacent mainline track pulling a short train. Doing this allows the Y6b to look the part so to speak. Whenever the Y6b is at the point of a mixed consist, I usually create the consist with six or so 50 ton scale hoppers behind the Y6, then several semi scale gons, flats, box, or tanks in a block of two or three ( running one semi scale gon, tank, flat or boxcar, looks out of balance ) which creates a balanced look to the overall train. The Y6b also looks great pulling a solid coal train of all 16 of my scale 50 ton coal hoppers ... and when I want to make this train longer I add 7 RK four bay hoppers at the front of the consist or interspersed throughout the consist and it all looks fine .. at least to my eye and those of my visitors.
I also have a set of the MPC era B&O Lionel RDC cars which I run during commuter rush hours along with my K Line Pennsy MU cars. Both the Lionel and K Line are semi scale and look great whizzing around the layout which has scale buildings pretty much.... and with scale freight cars sitting on sidings.
On my Mountain Division I can run all semi scale because this elevation is higher and farther away from the views eye. Using semi scale creates a forced perspective. This is where I pull out the Lionel 2--6-2 steamer from 1946/47 and put her to work, or my 2065 Lionel Hudson, my first train set I received from Santa in 1957 ( that was a wonderful Christmas!!!! ). I can also use my RK Dockside with a semi scale weathered flat with a log load and a RK bobber caboose. Sometimes I run a RK SW 1 with scale 50 ton coal hopper and a semi scale boxcar. Depends on the day.