I am planning a trip to Provence. I would like to know which is preferable to use as a base for some travel in Provence.

Also could someone recommend a clean, safe hotel in these cities?

Will you have a car? Or will you be relying on public transportation? If no car, Avignon is the better base as it has more transportation options.

How long will you be in Provence? I stayed three nights in Avignon and saw the city and took day trips to Arles and Isle sur la Sorgue by public bus. Then I picked up a car at the Avignon train station and based in the town of St. Remy for five days and zipped around the Luberon hill towns. IMO, it's easier to get into/out of and to park in a smaller town.
Ann Marie

As far as hotels, knowing your budget would be helpful.
Ann Marie

avignon is better train centre (as mentioned above), http://www.hotelmedieval.com/ (2 star but classy) was ok for us and very quiet

If you rent a car, Arles is a very nice base for traveling around Provence.

We spent two weeks based in Arles in 2011 and it was wonderful. We did have a car, though.

Bookmarking

I just got back from Provence 2 weeks ago, and before my trip, I had the same question you are asking now. I chose Avignon as my base for 3 nights, and am totally satisfied with my choice. I did not rent a car. I stayed at Hotel Central, and loved it. Great price, very friendly staff, clean, fantastic location 5 minutes from Centre Ville train station and the TI is very close too:
http://avignon-central-hotel.com/
Have a great trip!

It is a matter of taste. Both cities make convenient bases and both cities have major attractions which can reached by walking.

Arles has more small town feeling but is more touristy than Avignon.

Avignon has more restaurant choices and is much better for shopping.

For hotel search, use one of the common search engines, e.g. booking.com or hrs.com