I run a 536 and a 436 off the same instance of Sentinel, although you could run it on two different computers if you wished. What you probably should do so that things don't get confused between the two radios is create two different profiles within Sentinel, and be really diligent about changing to the right profile before doing anything relating to one radio or the other.
One thing that's important to remember is that the profiles are different between the two scanners (so long as you load one or the other before working with the different radios), but the favorite lists are not. Think of the favorite lists as being in a basket that either radio can take from. If one radio changes the contents of the basket (by deleting something from/changing something in a favorites list), the other radio will experience the same changes. There's been some cases where people have deleted favorites lists, or changed avoids/removed channels/etc from within FLs, because their 536 doesn't need that, and didn't realize that their 436 would be affected.
Profiles are managed through the File menu (New, Open, Save, etc) and the Edit>Edit Profile menu. A Profile can have different configuration inside the Edit Profile menu, including choosing what FLs the Profile "sees" or uses, but anything modified in the main screen of Sentinel is applied to all favorites lists globally.