Dear Ayelet,
This is not the kind of question which rabbis relish, but there you have it.
Although your sister presumably sees the ketubah and your participation in it as a way of adding Jewish features to her wedding and marriage, I cannot recommend your involvement as a signatory. You need to tread a path between showing support and love for your sister on the one hand and formally endorsing this (Jewishly illicit) union on the other. Signing her ketubah strays too far from this path. If you are to give a speech at the wedding you should avoid conventional expression of approbation and celebration such as “mazal tov”. Of course you can wish the couple happiness and good health, etc. Again, you will have to tread carefully.
At the same time, you must consider this: your sister’s choice of a husband is born of love (I am presuming), not out of rebellion (as you have confirmed). Moreover, the children born of this union will be Jewish, and your sister’s relationship with her Judaism will be a crucial factor in their prospects for their own Jewish identity and even upbringing. For this reason I would apply here the words of the Talmud (Sota 47a), “push away with the left hand and draw near with the right.”
I hope this is helpful.
Rabbi Rashi Simon