Selective mocking

var fakeObj1 = Isolate.Fake.Instance<Obj1Class>(Members.CallOriginal);
Isolate.WhenCalled(() => fakeObj1.Check(null)).WillReturn(true);
// Now we need to use a setter or some method to replace obj1
obj1 = fakeObj1;

If I understand correctly all you want is that the DoUsefulThing will be called but some methods such as obj1.Check won't be called?

it seems that obj1..obj5 are fields in your class so you need to replace them with a fake object created with CallOriginal with only the desired function set to return a predefined value.

public class MyClass
{
   private TestFoo obj1;
   private TestFoo obj2;
   private TestFoo obj3;
   private TestFoo obj4;
   private TestFoo obj5;

   public MyClass()
   {
      obj1 = Factory.Create(1);
      obj2 = Factory.Create(2);
      obj3 = Factory.Create(3);
      obj4 = Factory.Create(4);
      obj5 = Factory.Create(5);
   }
   public Result DoUsefulThing(
      string s1, string s2, string s3, string s4, string s5)
   { ... }
}

[Test]
public void Scenario3()
{
   var fakeObj1 = Isolate.Fake.Instance<MyClass>(Members.CallOriginal);
   var fakeObj2 = Isolate.Fake.Instance<MyClass>(Members.CallOriginal);
   var fakeObj3 = Isolate.Fake.Instance<MyClass>(Members.CallOriginal);
   var fakeObj4 = Isolate.Fake.Instance<MyClass>(Members.CallOriginal);
   var fakeObj5 = Isolate.Fake.Instance<MyClass>(Members.CallOriginal);
   
   Isolate.WhenCalled(() => fakeObj3.Get(null)).WillReturn(new MyClass.TestBar("phake"));
   Isolate.WhenCalled(() => fakeObj3.Check(null)).WillReturn(false);
   
   Isolate.Swap.NextInstance<MyClass>().With(fakeObj1);
   Isolate.Swap.NextInstance<MyClass>().With(fakeObj2);
   Isolate.Swap.NextInstance<MyClass>().With(fakeObj3);
   Isolate.Swap.NextInstance<MyClass>().With(fakeObj4);
   Isolate.Swap.NextInstance<MyClass>().With(fakeObj5);

   var t = new MyClass();
   var r = t.DoUsefulThing("symbols1", "symbols2", "symbols3", "symbols4", "symbols5");
   Assert.AreEqual(r, new MyClass.Result("something very bad"));
}