Would it be all right to have my sister, who was maid of honor for my first wedding, be matron of honor for my second wedding? She is still my best friend, and I can't imagine being married without her with me but don't want it to seem odd or uncomfortable for her.
It would be absolutely fine! All you need to do is ask your sister, making sure she is comfortable with the idea. You might tell her that you would feel so fortunate to have her by your side, supporting you and welcoming her new brother-in-law. Your upcoming wedding is not a flashback or replica of your first wedding. It's a fresh start, and who better to have with you than your best friend, who also happens to be your sister.
Would it be appropriate to ask my mother (my best friend who has been through everything with me, including an awful divorce) to be my matron of honor? I cannot think of anyone else I would rather have by my side.
Sure, it's perfectly appropriate to have your mom as your matron of honor. Talk it over with her, though, since she may feel she has a lot of responsibilities as mother-of-the-bride that would make it hard for her to be a 100 percent attentive matron of honor. If she decides both "jobs" are just too much to juggle, you will both know, nonetheless, that she will be your side in spirit, with great love for you, feeling very honored by your suggestion.