How big are the lenses your wife uses, and does she usually work on or off a tripod? I find that lenses over 500g are nose heavy on the K-S1, and the small grip becomes an issue. If you are shooting from a tripod, the point is moot, but then you have to be aware that the SD-card slot is in the bottom, and that can become inconvenient (especially if your tripod mounting plate blocks the bottom hatch). Also, do you have or are you planning to get any DA Limited lenses? The K-S1 loves the little lenses.
If you have a K-3, then you pretty much know how a K-5 is going to handle. After the K-r, Pentax juggled the buttons and 4-way controller layout on the low-end bodies. It's the same on the K-50 and K-S1, while the K-5 is the same as the K-3. If you go with the K-50 or K-S1, you will have three different button layouts in the family - this could be an issue if you are trying to help the kids with something. All three choices have 100% viewfinders, which is also a bit of a change from the K-r. The K-r's AF can be a little quriky (at least mine was), so any of the three choices are probably an improvement.
The K-S1 is more of an entry-level feature set, but if the K-r met your needs, then in terms of IQ, AF, and LiveView performance, I think the K-S1 is a big step up in every area. Compared to the K-r, the K-S1 lacks interval or multiple exposure shooting, but adds FluCard support. K-5IIs versus K-50: K-5IIs has better IQ and all the high-end features (like the buttery-soft shutter sound). In terms of size, the dimension differences between the K-5IIs and K-50 are negligible - but the weight difference is not. K-50 is 14% lighter, has marginally better AF & video, and has focus peaking in LiveView. K-5 shares battery with K-3, K-50 shares batteries with K-r. K-5IIs versus K-S1: K-5IIs has better IQ in low light, and has weather sealing and all the high-end features. K-S1 is smaller & 27% lighter, might have an IQ edge in good light (I don't want to get into 12-bit RAW versus 14-bit RAW and 20MP versus 16MP), has faster AF motor, probably better video, and focus peaking in LiveView. K-S1 shares lithium battery with K-r, but not AA batteries. K-50 versus K-S1: K-50 has weather sealing and a few other high-end features, and probably better IQ in low light. K-S1 is smaller and 14% lighter, has slightly better IQ in good light, and faster AF motor. EIther can share Li batteries with the K-r, but only the K-50 can share the AA battery clip.
I don't think there is a bad choice here. They are all very capable cameras, just with slightly different feature sets.
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